1. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31-46. doi:10.1158/2159-8290.CD-21-1059.

2. Institute of Medicine. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington (DC): National Academies Press; 2013. doi:10.17226/18359.

3. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC): National Academy Press; 2001. doi:10.17226/10027.

4. Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-742. doi:10.1056/NEJMoa1000678.

5. Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96-112. doi:10.1200/JCO.2016.70.1474.

6. Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA. 2017;318(2):197-198. doi:10.1001/jama.2017.7156.

7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. doi:10.1016/j.cell.2011.02.013.

8. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546-1558. doi:10.1126/science.1235122.

9. Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7(5):1016-1036.

10. Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23-28. doi:10.1126/science.959840.

11. Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306-313. doi:10.1038/nature10762.

12. McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168(4):613-628. doi:10.1016/j.cell.2017.01.018.

13. Martinez P, Baghli I, Gourjon G, Seyfried TN. Mitochondrial-stem cell connection: providing additional explanations for understanding cancer. Metabolites. 2024;14(4):229. doi:10.3390/metabo14040229.

14. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309-314. doi:10.1126/science.123.3191.309.

15. Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23(1):27-47. doi:10.1016/j.cmet.2015.12.006.

16. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2(5):e1600200. doi:10.1126/sciadv.1600200.

17. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-1437. doi:10.1038/nm.3394.

18. Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348(6230):74-80. doi:10.1126/science.aaa6204.

19. Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011;17(3):320-329. doi:10.1038/nm.2328.

20. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329-360. doi:10.1146/annurev.immunol.22.012703.104803.

21. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56-61. doi:10.1126/science.aaa8172.

22.Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol. 2006;90:1-50. doi:10.1016/S0065-2776(06)90001-7

23. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. doi:10.1126/science.aar4060.

24. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860-867. doi:10.1038/nature01322.

25. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-444. doi:10.1038/nature07205.

26. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-899. doi:10.1016/j.cell.2010.01.025.

27. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182-1186. doi:10.1056/NEJM197111182852108.

28. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7(9):987-989. doi:10.1038/nm0901-987.

29. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298-307. doi:10.1038/nature10144.

30. Fidler IJ. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3(6):453-458. doi:10.1038/nrc1098.

31. Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-284. doi:10.1038/nrc2622.

32. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168(4):670-691. doi:10.1016/j.cell.2016.11.037.

33. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53:615-627. doi:10.1146/annurev.med.53.082901.103929.

34. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714-726. doi:10.1038/nrc3599.

35. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69-80. doi:10.1016/j.cell.2010.02.027.

36. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730-737. doi:10.1038/nm0797-730.

37. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111. doi:10.1038/35102167.

38. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23(10):1124-1134. doi:10.1038/nm.4409.

39. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-6. doi:10.1136/bmj.39489.470347.AD.

40. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions. Version 6.5. Cochrane; 2024.

41. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372. doi:10.1136/bmj.n71.

42. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340. doi:10.1136/bmj.c332.

43. Sterne JAC, SavovićJ, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366. doi:10.1136/bmj.l4898.

44. Sterne JA, Hernán MA, Reeves BC, SavovićJ, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355. doi:10.1136/bmj.i4919.

45. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al., eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.

46. WHO Classification of Tumors Editorial Board. WHO Classification of Tumors Series. 5th ed. Lyon (France): International Agency for Research on Cancer; 2019-2024.

47. Febbo PG, Ladanyi M, Aldape KD, De Marzo AM, Hammond ME, Hayes DF, et al. NCCN Task Force report: evaluating the clinical utility of tumor markers in oncology. J Natl Compr Canc Netw. 2011;9 Suppl 5:S1-S32; quiz S33.

48. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026.

49. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S-150S. doi:10.2967/jnumed.108.057307.

50. O’Connor JPB, Aboagye EO, Adams JE, Aerts HJWL, Barrington SF, Beer AJ, et al. Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol. 2017;14(3):169-186. doi:10.1038/nrclinonc.2016.162.

51. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031-1037. doi:10.1056/NEJM200104053441401.

52. Chakravarty D, Gao J, Phillips SM, Kundra R, Zhang H, Wang J, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017; 2017:PO.17.00011. doi:10.1200/PO.17.00011.

53. Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol. 2018;29(9):1895-1902. doi:10.1093/annonc/mdy263.

54. Esteva A, Robicquet A, Ramsundar B, Kuleshov V, DePristo M, Chou K, et al. A guide to deep learning in healthcare. Nat Med. 2019;25(1):24-29. doi:10.1038/s41591-018-0316-z.

55. Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44-56. doi:10.1038/s41591-018-0300-7.

56. Kelly CJ, Karthikesalingam A, Suleyman M, Corrado G, King D. Key challenges for delivering clinical impact with artificial intelligence. BMC Med. 2019;17:195. doi:10.1186/s12916-019-1426-2.

57. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233-1241. doi:10.1056/NEJMoa022152.

58. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378(9804):1707-1716. doi:10.1016/S0140-6736(11)61629-2.

59. DeVita VT Jr, Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68(21):8643-8653. doi:10.1158/0008-5472.CAN-07-6611.

60. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792. doi:10.1056/NEJM200103153441101.

61. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. doi:10.1056/NEJMoa1003466.

62. Basch E, Deal AM, Kris MG, Scher HI, Hudis CA, Sabbatini P, et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol. 2016;34(6):557-565. doi:10.1200/JCO.2015.63.0830.

63. Mao JJ, Ismaila N, Bao T, Barton D, Ben-Arye E, Garland EL, et al. Integrative medicine for pain management in oncology: Society for Integrative Oncology-ASCO guideline. J Clin Oncol. 2022;40(34):3998-4024. doi:10.1200/JCO.22.01357.

64. Schilsky RL. Personalized medicine in oncology: the future is now. Nat Rev Drug Discov. 2010;9(5):363-366. doi:10.1038/nrd3181.

65. Meric-Bernstam F, Johnson A, Holla V, Bailey AM, Brusco L, Chen K, et al. A decision support framework for genomically informed investigational cancer therapy. J Natl Cancer Inst. 2015;107(7):djv098. doi:10.1093/jnci/djv098.

66. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. 2012;27(10):1361-1367. doi:10.1007/s11606-012-2077-6.

67. Zafar SY, Peppercorn JM, Schrag D, Taylor DH, Goetzinger AM, Zhong X, et al. The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. Oncologist. 2013;18(4):381-390. doi:10.1634/theoncologist.2012-0279.

68. Ramsey SD, Bansal A, Fedorenko CR, Blough DK, Overstreet KA, Shankaran V, et al. Financial insolvency as a risk factor for early mortality among patients with cancer. J Clin Oncol. 2016;34(9):980-986. doi:10.1200/JCO.2015.64.6620.

69. Altice CK, Banegas MP, Tucker-Seeley RD, Yabroff KR. Financial hardships experienced by cancer survivors: a systematic review. J Natl Cancer Inst. 2017;109(2):djw205. doi:10.1093/jnci/djw205.

70. Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer. 2008;44(17):2546-2554. doi:10.1016/j.ejca.2008.07.038.

71. Datta NR, Puric E, Klingbiel D, Gómez S, Bodis S. Hyperthermia and radiation therapy in locoregional recurrent breast cancers: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2016;94(5):1073-1087. doi:10.1016/j.ijrobp.2015.12.361.

72. Datta NR, Rogers S, Ordóñez SG, Puric E, Bodis S. Hyperthermia and radiotherapy in the management of head and neck cancers: a systematic review and meta-analysis. Int J Hyperthermia. 2016;32(1):31-40. doi:10.3109/02656736.2015.1099746.

73. Jones EL, Oleson JR, Prosnitz LR, Samulski TV, Vujaskovic Z, Yu D, et al. Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol. 2005;23(13):3079-3085. doi:10.1200/JCO.2005.05.520.

74. van der Zee J. Heating the patient: a promising approach? Ann Oncol. 2002;13(8):1173-1184. doi:10.1093/annonc/mdf280.

75. Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2016;(4):CD005005. doi:10.1002/14651858.CD005005.pub4.

76. Clarke RE, Tenorio LMC, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008;72(1):134-143. doi:10.1016/j.ijrobp.2007.12.048.

77. Feldmeier JJ, ed. Hyperbaric Oxygen 2003: Indications and Results: The Hyperbaric Oxygen Therapy Committee Report. Kensington, MD: Undersea and Hyperbaric Medical Society; 2003.

78. Hampson NB, ed. Hyperbaric Oxygen Therapy: 1999 Committee Report. Kensington, MD: Undersea and Hyperbaric Medical Society; 1999.

79. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688-694. doi:10.1038/nm1577.

80. Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen: comprehensive review of 321 original articles. Med Gas Res. 2015;5:12. doi:10.1186/s13618-015-0035-1.

81. Nicolson GL, de Mattos GF, Settineri R, Costa C, Ellithorpe R, Rosenblatt S, et al. Clinical effects of hydrogen administration: from animal and human diseases to exercise medicine. Int J Clin Med. 2016;7:32-76. doi:10.4236/ijcm.2016.71005.

82. Slezak J, Kura B, LeBaron TW, Singal PK, Buday J, Barancik M. Oxidative stress and pathways of molecular hydrogen effects in medicine. Curr Pharm Des. 2021;27(5):610-625. doi:10.2174/1381612826666200821114016.

83. Dolmans DEJGJ, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003;3(5):380-387. doi:10.1038/nrc1071.

84. Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61(4):250-281. doi:10.3322/caac.20114.

85. Allison RR, Moghissi K. Photodynamic therapy (PDT): clinical practice and future directions. Photodiagnosis Photodyn Ther. 2013;10(4):331-341. doi:10.1016/j.pdpdt.2013.08.001.

86. Lucky SS, Soo KC, Zhang Y. Nanoparticles in photodynamic therapy. Chem Rev. 2015;115(4):1990-2042. doi:10.1021/cr5004198.

87. Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol. 1992;55(1):145-157. doi:10.1111/j.1751-1097.1992.tb04222.x.

88. Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, Charboneau JW, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria—10-year update. J Vasc Interv Radiol. 2014;25(11):1691-1705.e4. doi:10.1016/j.jvir.2014.08.027.

89. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN. Principles of and advances in percutaneous ablation. Radiology. 2011;258(2):351-369. doi:10.1148/radiol.10081634.

90. Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, et al. Sustained complete response and complications after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Radiology. 2008;246(3):963-971. doi:10.1148/radiol.2463070586.

91. Gervais DA, McGovern FJ, Wood BJ, Goldberg SN, McDougal WS, Mueller PR. Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology. 2003;226(2):417-424. doi:10.1148/radiol.2262012062.

92. Tempany CMC, Stewart EA, McDannold N, Quade BJ, Jolesz FA, Hynynen K. Focused ultrasound surgery in oncology: a review. J Am Coll Radiol. 2011;8(2):39-44. doi:10.1016/j.jacr.2010.07.004.

93. Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumors. Nat Rev Cancer. 2005;5(4):321-327. doi:10.1038/nrc1591.

94. Zhou YF. High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol. 2011;2(1):8-27. doi:10.5306/wjco.v2.i1.8.

95. Wu F, Wang ZB, Zhu H, Chen WZ, Zou JZ, Bai J, et al. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer. J Surg Oncol. 2005;92(3):209-213.

96. Mohan R, Grosshans D. Proton therapy—present and future. Adv Drug Deliv Rev. 2017;109:26-44. doi:10.1016/j.addr.2016.11.006.

97. Newhauser WD, Zhang R. The physics of proton therapy. Phys Med Biol. 2015;60(8):R155-R209. doi:10.1088/0031-9155/60/8/R155.

98. Mitin T, Zietman AL. Promise and pitfalls of heavy-particle therapy. J Clin Oncol. 2014;32(26):2855-2863. doi:10.1200/JCO.2014.55.1945.

99. Paganetti H. Proton therapy physics. Med Phys. 2012;39(3):1430-1444. doi:10.1118/1.3682259.

100. Herrmann K, Schwaiger M, Lewis JS, Solomon SB, McNeil BJ, Baumann M, et al. Radiotheranostics: a roadmap for future development. Lancet Oncol. 2020;21(3):e146-e156. doi:10.1016/S1470-2045(19)30821-6.

101. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322.

102. Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of ^177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427.

103. Herrmann K, Larson SM, Weber WA. Theranostic concepts: more than just a buzzword. J Nucl Med. 2017;58 Suppl 2:1S-2S. doi:10.2967/jnumed.116.186403.

104. Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, et al. ^225Ac-PSMA-617 for PSMA-targeted α therapy of metastatic castration-resistant prostate cancer. J Nucl Med. 2016;57(12):1941-1944. doi:10.2967/jnumed.116.178673. Journal of Nuclear Medicine.

105. June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):1361-1365. doi:10.1126/science.aar6711.

106. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-448. doi:10.1056/NEJMoa1709866.

107. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447.

108. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62-68. doi:10.1126/science.aaa4967.

109. Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666. doi:10.1200/JCO.21.00612.

110. Finn OJ. Cancer vaccines: between the idea and the reality. Nat Rev Immunol. 2003;3(8):630-641. doi:10.1038/nri1150.

111. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422. doi:10.1056/NEJMoa1001294.

112. Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222-226. doi:10.1038/nature23003.

113. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217-221. doi:10.1038/nature22991.

114. Vogl TJ, Naguib NNN, Nour-Eldin NEA, Rao P, Emad-Eldin S, Zangos S, et al. Review on transarterial chemoembolization and radioembolization of hepatocellular carcinoma: current practice and future developments. World J Gastroenterol. 2011;17(17):3410-3424.

115. Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734-1739. doi:10.1016/S0140-6736(02)08649-X.

116. Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151(6):1155-1163.e2. doi:10.1053/j.gastro.2016.08.029.

117. Meric-Bernstam F, Mills GB. Overcoming implementation challenges of personalized cancer therapy. Nat Rev Clin Oncol. 2012;9(9):542-548. doi:10.1038/nrclinonc.2012.127.

118. Ioakeim-Skoufa I, Tobajas-Ramos N, Menditto E, Aza-Pascual-Salcedo M, Gimeno-Miguel A, Orlando V, et al. Drug repurposing in oncology: a systematic review of randomized controlled clinical trials. Cancers (Basel). 2023;15(11):2972. doi:10.3390/cancers15112972.

119. Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, et al. Effect of metformin versus placebo on invasive disease-free survival in patients with breast cancer: the MA.32 randomized clinical trial. JAMA. 2022;327(20):1963-1973. doi:10.1001/jama.2022.6147.

120. Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG, et al. Insulin-lowering effects of metformin in women with early breast cancer. Clin Breast Cancer. 2008;8(6):501-505. doi:10.3816/CBC.2008.n.060.

121. Cazzaniga M, DeCensi A, Pruneri G, Puntoni M, Guerrieri-Gonzaga A, Johansson H, et al. The effect of metformin on pathological response and survival in breast cancer patients treated with neoadjuvant chemotherapy: a randomized trial. Breast Cancer Res Treat. 2013;140(2):387-397.

122. Dowling RJO, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007;67(22):10804-10812. doi:10.1158/0008-5472.CAN-07-2310.

123. Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330(7503):1304-1305. doi:10.1136/bmj.38415.708634.F7.

124. Lord SR, Harris AL. Is it still worth pursuing the repurposing of metformin as a cancer therapeutic? Br J Cancer. 2023;128(6):958-966. doi:10.1038/s41416-023-02204-2.

125. Foretz M, Guigas B, Viollet B. Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023;19(8):460-476. doi:10.1038/s41574-023-00833-4.

126. Wu Z, Wang W, Wei L, Zhu S. Current status and frontier tracking of clinical trials on metformin for cancer treatment. J Cancer Res Clin Oncol. 2023;149(18):16931-16946. doi:10.1007/s00432-023-05391-w.

127. Yu OHY, Suissa S. Metformin and cancer: solutions to a real-world evidence failure. Diabetes Care. 2023;46(5):904-912. doi:10.2337/dci22-0047.

128. Grabacka M, Plonka PM, Urbanska K, Reiss K. Peroxisome proliferator-activated receptor αactivation decreases metastatic potential of melanoma cells in vitro via down-regulation of Akt. Clin Cancer Res. 2006;12(10):3028-3036. doi:10.1158/1078-0432.CCR-05-2532.

129. Saidi SA, Holland CM, Charnock-Jones DS, Smith SK. In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer. Mol Cancer. 2006;5:13. doi:10.1186/1476-4598-5-13.

130. Peters JM, Shah YM, Gonzalez FJ. The role of peroxisome proliferator-activated receptor-αin carcinogenesis. Toxicol Sci. 2012;126(1):1-18.

131. Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab. 2012;23(7):351-363. doi:10.1016/j.tem.2012.05.001.

132. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367(19):1792-1802. doi:10.1056/NEJMoa1201735.

133. Cardwell CR, Hicks BM, Hughes C, Murray LJ. Statin use after colorectal cancer diagnosis and survival: a population-based cohort study. J Clin Oncol. 2014;32(28):3177-3183. doi:10.1200/JCO.2013.54.4569.

134. Cholesterol Treatment Trialists’ (CTT) Collaboration. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One. 2012;7(1):e29849. doi:10.1371/journal.pone.0029849.

135. Shokr H, Liao WC, Faivre-Finn C, Dempsey C, Williams KJ, Chen LC. Impact of statin use on survival and adverse events in patients with cancer receiving radiotherapy: a systematic review and meta-analysis. BMC Cancer. 2025;25(1):1666. doi:10.1186/s12885-025-15038-3.

136. Yang J, Lin J, Guo H, Wu W, Wang J, Mao J, et al. Administration of statins is correlated with favourable prognosis in lung cancer patients receiving immune checkpoint inhibitors. Front Immunol. 2025;16:1638677. doi:10.3389/fimmu.2025.1638677.

137. Burn J, Gerdes AM, Macrae F, Mecklin JP, Möslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081-2087. doi:10.1016/S0140-6736(11)61049-0.

138. Burn J, Sheth H, Elliott F, Reed L, Macrae F, Mecklin JP, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet. 2020;395(10240):1855-1863. doi:10.1016/S0140-6736(20)30366-4.

139. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741-1750. doi:10.1016/S0140-6736(10)61543-7.

140. Rothwell PM, Price JF, Fowkes FGR, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379(9826):1602-1612. doi:10.1016/S0140-6736(11)61720-0.

141. Chia JWK, Segelov E, Deng Y, Ho GF, Wang W, Han S, et al. Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2025;10(3):198-209. doi:10.1016/S2468-1253(24)00387-X.

142. Hoang KD, Chen JH, Huang TW, Kang YN, Chen C. Oral aspirin for preventing colorectal adenoma recurrence: a systematic review and network meta-analysis of randomized controlled trials. PLoS One. 2024;19(3):e0279784. doi:10.1371/journal.pone.0279784.

143. Benjamin DJ, Haslam A, Prasad V. Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: a systematic review and meta-analysis of randomized trials. Cancer Med. 2024;13(5):e7049. doi:10.1002/cam4.7049.

144. Juarez M, Schcolnik-Cabrera A, Dueñas-González A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.

145. Sharmeen S, Skrtic M, Sukhai MA, Hurren R, Gronda M, Wang X, et al. The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. Blood. 2010;116(18):3593-3603. doi:10.1182/blood-2010-01-262675.

146. Dou Q, Chen HN, Wang K, Yuan K, Lei Y, Li K, et al. Ivermectin induces cytostatic autophagy by blocking the PAK1/Akt axis in breast cancer. Cancer Res. 2016;76(15):4457-4469. doi:10.1158/0008-5472.CAN-15-2887.

147. Hashimoto H, Messerli SM, Sudo T, Maruta H. Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines. Drug Discov Ther. 2009;3(6):243-246.

148. Zhang X, Liu Y, Chen L, et al. Ivermectin inhibits tumor growth and enhances chemosensitivity in colorectal cancer via ROS-mediated mitochondrial apoptosis. Cell Death Dis. 2021;12:112.

149. Draganov D, Lee S, Wang X, et al. Ivermectin induces immunogenic cell death and synergizes with anti-PD-1 in triple-negative breast cancer. Oncoimmunology. 2022;11:2045312.

150. Jiménez-Gaona Y, Vivanco-Galván O, Morales-Larreategui G, Cabrera-Bejarano A, Lakshminarayanan V. Outcome of ivermectin in cancer treatment: an experience in Loja-Ecuador. Nurs Rep. 2023;13(1):315-326. doi:10.3390/nursrep13010030.

151. Bossaer JB, Gerber DE, Morris RE, Burton J, et al. Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: results of a phase 1 clinical trial. J Neurooncol. 2021;153:113-121.

152. Bai RY, Staedtke V, Aprhys CM, Gallia GL, Riggins GJ. Anti-parasitic mebendazole shows survival benefit in two preclinical models of glioblastoma multiforme. Neuro Oncol. 2011;13(9):974-982.

153. De Witt M, Gamble A, Hanson D, Markowitz D, Powell C, Al Dimassi S, et al. Repurposing mebendazole as a replacement for vincristine for the treatment of brain tumors. Mol Med. 2017;23:50-56. doi:10.2119/molmed.2017.00011.

154. Dobrosotskaya IY, Hammer GD, Schteingart DE, Maturen KE, Worden FP. Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma. Endocr Pract. 2011;17(3):e59-e62. doi:10.4158/EP10390.CR.

155. Hegazy SK, El-Azab GA, Zakaria F, Mostafa MF, El-Ghoneimy RA. Mebendazole: from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer. Life Sci. 2022;299:120536. doi:10.1016/j.lfs.2022.120536.

156. Nygren P, Larsson R. Repositioning of mebendazole as an anticancer drug: from bench to bedside. Ups J Med Sci. 2020;125(2):93-101.

157. Hulscher N, Victory K, Thorp JA, Pinsky D, Diaz-Villalobos A, Gillooly P, et al. Real-world clinical outcomes of ivermectin and mebendazole in cancer patients: results from a prospective observational cohort. Anticancer Res. 2026;46(6):3243-3255. doi:10.21873/anticanres.18194. Expression of concern published: Anticancer Res. 2026;46(6):e3243. doi:10.21873/anticanres.18276.

158. Dogra N, Kumar A, Mukhopadhyay T. Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways. Sci Rep. 2018;8:11926. doi:10.1038/s41598-018-30158-6.

159. Dogra N, Mukhopadhyay T. Impairment of the ubiquitin-proteasome pathway by methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate leads to a potent cytotoxic effect in tumor cells. Int J Cancer. 2012;130(6):1217-1228.

160. Loo TW, Clarke DM. Selective disruption of P-glycoprotein function by ivermectin and other anti-parasitic agents. Biochem Pharmacol. 2002;63(11):199-202.

161. Mukherjee S, Kumar R, Singh A. Fenbendazole as a repurposed anthelmintic with anticancer properties: mechanisms and preclinical evidence. Front Pharmacol. 2022;13:892341.

162. Son DS, Lee ES, Adunyah SE. The antitumor potentials of benzimidazole anthelmintics as repurposing drugs. Immune Netw. 2020;20(4):e29. doi:10.4110/in.2020.20.e29.

163. Schweizer MT, Haugk K, McKiernan JS, Gulati R, Cheng HH, Maes JL, et al. A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer. PLoS One. 2018;13(6):e0198389. doi:10.1371/journal.pone.0198389.

164. Chen W, Mook RA Jr, Premont RT, Wang J. Niclosamide: beyond an antihelminthic drug. Cell Signal. 2018;41:89-96. doi:10.1016/j.cellsig.2017.04.001.

165. Sack U, Walther W, Scudiero D, Selby M, Kobelt D, Lemm M, et al. Novel effect of antihelminthic niclosamide on S100A4-mediated metastatic progression in colon cancer. J Natl Cancer Inst. 2011;103(13):1018-1036.

166. Li Y, Li PK, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ. Multi-targeted therapy of cancer by niclosamide: a new application for an old drug. Cancer Lett. 2014;349(1):8-14. doi:10.1016/j.canlet.2014.04.003.

167. Burock S, Daum S, Keilholz U, Neumann K, Walther W, Stein U. Phase II trial to investigate the safety and efficacy of orally applied niclosamide in patients with metachronous or synchronous metastases of a colorectal cancer progressing after therapy: the NIKOLO trial. BMC Cancer. 2018;18:297. doi:10.1186/s12885-018-4197-9.

168. Karasic TB, O’Hara MH, Loaiza-Bonilla A, Reiss KA, Teitelbaum UR, Borazanci E, et al. Effect of gemcitabine and nab-paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5(7):993-998. doi:10.1001/jamaoncol.2019.0684.

169. Wolpin BM, Rubinson DA, Wang X, Chan JA, Cleary JM, Enzinger PC, et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014;19(6):637-638. doi:10.1634/theoncologist.2014-0086.

170. Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, et al. Combined mTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014;10(8):1391-1402. doi:10.4161/auto.29119.

171. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, et al. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 2007;117(2):326-336. doi:10.1172/JCI28833.

172. Cook KL, Wärri A, Soto-Pantoja DR, Clarke PA, Cruz MI, Zwart A, et al. Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res. 2014;20(12):3222-3232. doi:10.1158/1078-0432.CCR-13-3227.

173. Krishna S, Ganapathi S, Ster IC, Saeed MEM, Cowan M, Finlayson C, et al. A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine. 2015;2(1):82-90. doi:10.1016/j.ebiom.2014.11.010.

174. von Hagens C, Walter-Sack I, Goeckenjan M, Osburg J, Storch-Hagenlocher B, Sertel S, et al. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat. 2017;164(2):359-369. doi:10.1007/s10549-017-4261-1.

175. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. Int J Oncol. 2001;18(4):767-773. doi:10.3892/ijo.18.4.767.

176. Efferth T, Giaisi M, Merling A, Krammer PH, Li-Weber M. Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One. 2007;2(8):e693. doi:10.1371/journal.pone.0000693.

177. Strik H, Efferth T, Kaina B. Artesunate in glioblastoma therapy: case reports and review of clinical studies. Phytomedicine. 2024;123:155274. doi:10.1016/j.phymed.2023.155274.

178. Mukherjee S, Kumar R, Singh A. Artesunate as a repurposed antimalarial with anticancer properties: mechanisms and clinical progress. Front Pharmacol. 2023;14:1132647.

179. Antonarakis ES, Heath EI, Smith DC, Rathkopf D, Blackford AL, Danila DC, et al. Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer. Oncologist. 2013;18(2):163-173. doi:10.1634/theoncologist.2012-0314.

180. Rudin CM, Brahmer JR, Juergens RA, Hann CL, Ettinger DS, Sebree R, et al. Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2013;8(5):619-623. doi:10.1097/JTO.0b013e31828c3950.

181. Kim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell. 2010;17(4):388-399. doi:10.1016/j.ccr.2010.02.027.

182. Scatena C, Roncella M, Di Paolo A, Aretini P, Menicagli M, Fanelli G, et al. Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients: a clinical pilot study. Front Oncol. 2018;8:452. doi:10.3389/fonc.2018.00452.

183. Duivenvoorden WCM, PopovićSV, Lhoták Š, Seidlitz E, Hirte HW, Tozer RG, et al. Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res. 2002;62(6):1588-1591.

184. Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget. 2015;6(7):4569-4584. doi:10.18632/oncotarget.3174.

185. Onoda T, Ono T, Dhar DK, Yamanoi A, Fujii T, Nagasue N. Doxycycline inhibits cell proliferation and invasive potential: combination therapy with cyclooxygenase-2 inhibitor in human colorectal cancer cells. J Lab Clin Med. 2004;143(4):207-216. doi:10.1016/j.lab.2003.12.012.

186. Niesvizky R, Jayabalan D, Christos PJ, Furst JR, Naib T, Ely S, et al. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone): an effective regimen for newly diagnosed multiple myeloma. Blood. 2008;111(3):1101-1109.

187. Morris TCM, Kettle PJ, Drake M, Jones FCG, Hull DR, Boyd K, et al. Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. Br J Haematol. 2008;143(3):349-354. doi:10.1111/j.1365-2141.2008.07360.x.

188. Gregersen H, Do T, Kristensen IB, Frølund UC, Andersen NF, Nielsen LK, et al. A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma. Exp Hematol Oncol. 2018;7:25.

189. Niesvizky R, Coleman M, Mark T, et al. BiRD versus lenalidomide and low-dose dexamethasone in newly diagnosed multiple myeloma: a case-matched analysis. Br J Haematol. 2012;156(6):706-715.

190. Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, et al. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. doi:10.1002/ajh.21777.

191. Adams WJ, Morris DL. Short-course cimetidine and survival with colorectal cancer. Lancet. 1994;344(8934):1768-1769.

192. Links M, Clingan PR, Phadke K, O’Baugh J, Legge J, Adams WJ, et al. A randomized trial of cimetidine with 5-fluorouracil and folinic acid in metastatic colorectal cancer. Eur J Surg Oncol. 1995;21(5):523-525.

193. Kelly MD, King J, Cherian M, Dwerryhouse SJ, Finlay IG, King DW, et al. Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes. Cancer. 1999;85(7):1658-1663.

194. Matsumoto S, Imaeda Y, Umemoto S, Kobayashi K, Suzuki H, Okamoto T. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumor cells. Br J Cancer. 2002;86(2):161-167.

195. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.

196. Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in mice with neuroblastoma. Science. 1983;221(4611):671-673.

197. Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Integr Cancer Ther. 2009;8(4):416-422.

198. Patten DK, Schultz BG, Berlau DJ. Low-dose naltrexone therapy: a review of the evidence for use in chronic pain and other conditions. J Am Assoc Nurse Pract. 2018;30(4):182-187.

199. Malik A, Ye A, Chung M. Low dose naltrexone for refractory cancer pain: case series of initial safety and effectiveness. J Pain Symptom Manage. 2025;70(6):e492-e497. doi:10.1016/j.jpainsymman.2025.08.015.

200. Hiller JG, Cole SW, Crone EM, Byrne DJ, Shackleford DM, Pang JM, et al. Preoperative β with propranolol reduces biomarkers of metastasis in breast cancer: a phase II randomized trial. Clin Cancer Res. 2020;26(8):1803-1811.

201. Shaashua L, Shabat-Simon M, Haldar R, Matzner P, Zmora O, Shabtai M, et al. Perioperative COX-2 and β blockade improves metastatic biomarkers in breast cancer patients. Clin Cancer Res. 2017;23(16):4651-4661.

202. Pantziarka P, Bouche G, Sukhatme V, Meheus L, Sukhatme VP. Repurposing drugs in oncology (ReDO)—beta-blockers as anti-cancer agents. Ecancermedicalscience. 2016;10:680.

203. Barron TI, Flahavan EM, Sharp L, Bennett K, Visvanathan K. Recent use of β and breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat. 2011;130(2):939-949.

204. Murphy JE, Wo JY, Ryan DP, Clark JW, Jiang W, Yeap BY, et al. Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5(7):1020-1027. doi:10.1001/jamaoncol.2019.0892.

205. Ramaswamy A, Bhargava P, Gota V, Srinivas S, Sultana N, Mandavkar S, et al. Efficacy of losartan plus modified FOLFIRINOX versus modified FOLFIRINOX in advanced pancreatic cancers: A randomized clinical trial (AFPAC Study). Cancer. 2025 Jul 1;131(13):e35945. doi:10.1002/cncr.35945.

206. Diop-Frimpong B, Chauhan VP, Krane S, Boucher Y, Jain RK. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proc Natl Acad Sci U S A. 2011;108(7):2909-2914.

207. Nechushtan H, Hamamreh Y, Nidal S, Gotfried M, Baron A, Shalev YI, et al. A phase IIb trial assessing the addition of disulfiram to chemotherapy for the treatment of metastatic non-small cell lung cancer. Oncologist. 2015;20(4):366-367.

208. Skrott Z, Mistrik M, Andersen KK, Friis S, Majera D, Gursky J, et al. Alcohol-abuse drug disulfiram targets cancer via the p97 segregase adaptor NPL4. Nature. 2017;552(7684):194-199.

209. Brar SS, Grigg C, Wilson KS, Holder WD Jr, Dreau D, Austin C, et al. Disulfiram inhibits activating transcription factor/cAMP-responsive element binding protein and human melanoma growth in a metal-dependent manner. Mol Cancer Ther. 2004;3(9):1049-1060.

210. Werlenius K, Kinhult S, Solheim TS, Jakola AS, Rygh CB, Omdal RK, et al. Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma: A Randomized Clinical Trial. JAMA Netw Open. 2023 Mar 1;6(3):e234149. doi:10.1001/jamanetworkopen.2023.4149.

211. Steinbach G, Lynch PM, Phillips RKS, Wallace MH, Hawk E, Gordon GB, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342(26):1946-1952.

212. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355(9):873-884.

213. Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006;355(9):885-895.

214. Solomon SD, McMurray JJV, Pfeffer MA, Wittes J, Fowler R, Finn P, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352(11):1071-1080.

215. Bertagnolli MM, et al. New, long-term insights from the Adenoma Prevention with Celecoxib Trial on a promising but troubled class of drugs. Cancer Prev Res (Phila). 2009;2(4):285-292.

216. Grady WM, et al. Five-year analysis of the prevention of colorectal sporadic adenomatous polyps trial. J Natl Cancer Inst. 2011;103(11):872-881.

217. Spano D, Marshall JC, Marino N, De Martino D, Romano A, Scoppettuolo MN, et al. Dipyridamole prevents triple-negative breast-cancer progression. Clin Exp Metastasis. 2013;30(1):47-68.

218. Chong CR, Sullivan DJ Jr. New uses for old drugs. Nature. 2007;448(7154):645-646.

219. Pantziarka P, Bouche G, Sukhatme V, Meheus L, Sukhatme VP. Repurposing drugs in oncology: from candidate selection to clinical adoption. Semin Cancer Biol. 2021;68:186-191.

220. Isacoff WH, Benedetti JK, Barstis JL, Jazieh AR, Macdonald JS, Philip PA. Phase II trial of infusional 5-fluorouracil, leucovorin, mitomycin-C and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol. 2007;25(14):1665-1669.

221. Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003;21(13):2545-2550.

222. Gothard L, Cornes P, Earl J, Hall E, MacLaren J, Peach D, et al. Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer. Radiother Oncol. 2004;73(2):133-139.

223. Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol. 2004;73(2):119-131.

224. Magnusson M, Höglund P, Johansson K, Jönsson C, Killander F, Malmström P, et al. Pentoxifylline and vitamin E treatment for prevention of radiation-induced side-effects in women with breast cancer: a phase II randomized trial. Eur J Cancer. 2009;45(14):2488-2495.

225. Mehrzad V, Afshar R, Akbari M. Pentoxifylline treatment in patients with cancer cachexia: a double-blind, randomized, placebo-controlled clinical trial. Adv Biomed Res. 2016;5:45.

226. Tardivo JP, Del Giglio A, de Oliveira CS, Gabrielli DS, Junqueira HC, Tada DB, et al. Methylene blue in photodynamic therapy: from basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther. 2005;2(3):175-191. doi:10.1016/S1572-1000(05)00097-9.

227. Roldan CJ, Nouri K, Chai T, Huh B. Methylene blue for the treatment of intractable pain associated with oral mucositis. Pain Pract. 2017;17(8):1115-1121. doi:10.1111/papr.12566.

228. Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Antimicrob Chemother. 1998;42(1):13-28. doi:10.1093/jac/42.1.13.

229. Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of methylene blue in the nervous system. Med Res Rev. 2011;31(1):93-117. doi:10.1002/med.20177.

230. Pominova D, Ryabova A, Skobeltsin A, Markova I, Linkov K, Romanishkin I. The use of methylene blue to control the tumor oxygenation level. Photodiagnosis Photodyn Ther. 2024;46:104047. doi:10.1016/j.pdpdt.2024.104047.

231. da Veiga Moreira J, Schwartz L, Jolicoeur M. Singlet oxygen-induced mitochondrial reset in cancer: a novel approach for ovarian cancer therapy. Metabolites. 2024;14(12):648. doi:10.3390/metabo14120648.

232. Zhu T, Ding J, Zheng F, Fang Y, Huang W, Yin Y, et al. Synergistic cancer therapy: an NIR-activated methylene blue-nitrogen mustard prodrug for combined chemotherapy and photodynamic therapy. J Med Chem. 2025;68(7):7630-7641. doi:10.1021/acs.jmedchem.5c00120.

233. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008;19(11):1969-1974. doi:10.1093/annonc/mdn377.

234. Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, et al. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. doi:10.1371/journal.pone.0029794.

235. Welsh JL, Wagner BA, van’t Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, et al. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013;71(3):765-775. doi:10.1007/s00280-013-2070-8.

236. Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, et al. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024;77:103375. doi:10.1016/j.redox.2024.103375.

237. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, et al. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res. 2010;16(2):509-520. doi:10.1158/1078-0432.CCR-09-1713.

Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999.

Schoenfeld JD, Sibenaller VA, Mapuskar KP, et al. Radio- and chemo-sensitization by high-dose vitamin C in glioblastoma and non–small cell lung cancer models. Sci Transl Med. 2017.

Yun J, Muller S, Cairney C, et al. Vitamin C selectively kills KRAS-mutant colorectal cancer via GAPDH inhibition. Nature. 2015.

Du J, Cieslak JM, Wagner BA, Buettner GR, Schafer FQ, Levine M, et al. Mechanisms of ascorbate-induced cytotoxicity in cancer: Fenton chemistry and hydrogen peroxide generation. Cancer Res. 2010/2012.

Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbate induces hydrogen peroxide–mediated cytotoxicity in cancer cells. Proc Natl Acad Sci USA. 2005/2008.

National Cancer Institute. High-Dose Vitamin C (PDQ®)–Health Professional Version. Updated regularly.

Klimant E, et al. Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Curr Oncol. 2018;25(2):139–48.

Mikirova N, et al. Risk of high-dose intravenous vitamin C therapy in cancer patients. J Transl Med. 2007/2013.

Drisko J, et al. Pharmacokinetics of high-dose intravenous vitamin C. J Orthomol Med. 2003/2005.

Padayatty SJ, Chen Q, Levine M, Hoffer LJ. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010.

Zhao H, Zhu H, Huang J, Zhu Y, Hong M, Zhu H, Zhang J, Li S, Yang L, Lian Y, et al. The synergy of vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acute myeloid leukemia. Leuk Res. 2018;66:1–7.

Schoenfeld JD, Sibenaller VA, Mapuskar KP, Wagner BA, Cieslak JM, Du J, et al. A phase I/II trial of high-dose intravenous vitamin C with standard therapy in glioblastoma. Sci Transl Med. 2017.

Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6(222):222ra18.

Stephenson CM, Levin RD, Spector T, Oliver CG. Phase I clinical trials of high-dose intravenous ascorbate in patients with advanced malignancy. PLoS One. 2013.

Moertel CG, et al. High-dose vitamin C versus placebo in patients with advanced colorectal cancer. N Engl J Med. 1985.

Creagan ET, et al. Lack of efficacy of high-dose ascorbic acid therapy in advanced human cancer. N Engl J Med. 1979.

Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1978;75:4538–42.

Intravenous vitamin C associated with longer median overall survival in malignant neoplasm (moderate certainty). PubMed. 2025;40613397.

Zhao H, Fu W, Yang X, Zhang W, Wu S, Ma J, Zhang T, Yao H, Zhang Z. High-dose vitamin C: a promising anti-tumor agent, insight from mechanisms, clinical research, and challenges. Genes Dis. 2025;13(2):101742.

Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. J Exp Clin Cancer Res. 2021;40:343.

Carr AC, Cook J. Intravenous vitamin C for cancer therapy – identifying the current gaps in our knowledge. Front Physiol. 2018;9:1182.

Jacobs C, Hutton B, Cooley K, Seely D, Tsang R, Fritz H, et al. Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Curr Oncol. 2018;25(2):139–48.

Fritz H, Flower G, Weeks L, Cooley K, Seely D, Tsang R, et al. Intravenous vitamin C and cancer: a systematic review. Integr Cancer Ther. 2014;13(4):280–300.

261. Baghli I, Makis W, Marik PE, Gonzalez MJ, Grant WB, Hunninghake R, et al. Targeting the mitochondrial-stem cell connection in cancer treatment: a hybrid orthomolecular protocol. J Orthomol Med. 2024;39(3).

262. Al-Lazikani B, Banerji U, Workman P. Combinatorial drug therapy for cancer in the post-genomic era. Nat Biotechnol. 2012;30(7):679-692. doi:10.1038/nbt.2284.

263. Palmer AC, Sorger PK. Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy. Cell. 2017;171(7):1678-1691.e13. doi:10.1016/j.cell.2017.11.009.

264. Frei E 3rd. Curative cancer chemotherapy. Cancer Res. 1985;45(12 Pt 1):6523-6537.

265. Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022-38043. doi:10.18632/oncotarget.16723.

266. Prasad V, Fojo T, Brada M. Precision oncology: origins, optimism, and potential. Lancet Oncol. 2016;17(2):e81-e86. doi:10.1016/S1470-2045(15)00620-8.

267. Greenlee H, DuPont-Reyes MJ, Balneaves LG, Carlson LE, Cohen MR, Deng G, et al. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment. CA Cancer J Clin. 2017;67(3):194-232. doi:10.3322/caac.21397.

268. Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, et al. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol. 2015;35 Suppl:S276-S304. doi:10.1016/j.semcancer.2015.09.007.

269. Lyman GH, Greenlee H, Bohlke K, Bao T, DeMichele AM, Deng GE, Fouladbakhsh JM, Gil B, Hershman DL, Mansfield S, Mussallem DM, Mustian KM, Price E, Rafte E, Cohen L. Integrative therapies during and after breast cancer treatment: ASCO endorsement of the SIO clinical practice guideline. J Clin Oncol. 2018;36(25):2647-2655. doi:10.1200/JCO.2018.79.2721.

270. Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10(20):6847-6854.

271. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491-4499. doi:10.1158/1078-0432.CCR-08-0024.

272. Hewlings SJ, Kalman DS. Curcumin: a review of its effects on human health. Foods. 2017;6(10):92. doi:10.3390/foods6100092.

273. Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325-1348. doi:10.1111/bph.13621.

274. de Waure C, Bertola C, Baccarini G, Chiavarini M, Mancuso C. Exploring the contribution of curcumin to cancer therapy: a systematic review of randomized controlled trials. Pharmaceutics. 2023;15(4):1275. doi:10.3390/pharmaceutics15041275.

275. Chen YX, Gao QY, Zou TH, Wang BM, Liu SD, Sheng JQ, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020;5(3):267-275. doi:10.1016/S2468-1253(19)30409-1.

276. Tillhon M, Guamán Ortiz LM, Lombardi P, Scovassi AI. Berberine: new perspectives for old remedies. Biochem Pharmacol. 2012;84(10):1260-1267. doi:10.1016/j.bcp.2012.07.018.

277. Cicero AFG, Baggioni A. Berberine and its role in chronic disease. Adv Exp Med Biol. 2016;928:27-45. doi:10.1007/978-3-319-41334-1_2.

278. Habtemariam S. Berberine pharmacology and the gut microbiota: a hidden therapeutic link. Pharmacol Res. 2020;155:104722. doi:10.1016/j.phrs.2020.104722.

279. Tan YJ, Zou TH, Yu K, Sheng JQ, Jin P, Zhang MJ, et al. Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-year follow-up of a randomized clinical trial. Cell Rep Med. 2025;6(9):102293. doi:10.1016/j.xcrm.2025.102293.

280. Chow HHS, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and Polyphenon E. Cancer Epidemiol Biomarkers Prev. 2001;10(1):53-58.

281. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006;66(2):1234-1240. doi:10.1158/0008-5472.CAN-05-1145.

282. Kumar NB, Pow-Sang J, Egan KM, Spiess PE, Dickinson S, Salup R, et al. Randomized, placebo-controlled trial of green tea catechins for prostate cancer prevention. Cancer Prev Res (Phila). 2015;8(10):879-887. doi:10.1158/1940-6207.CAPR-14-0324.

283. Crew KD, Brown P, Greenlee H, Bevers TB, Arun B, Hudis C, et al. Phase IB randomized, double-blinded, placebo-controlled, dose escalation study of Polyphenon E in women with hormone receptor-negative breast cancer. Cancer Prev Res (Phila). 2012;5(9):1144-1154.

284. Shanafelt TD, Call TG, Zent CS, Leis JF, LaPlant B, Bowen DA, Roos M, Laumann K, Ghosh AK, Lesnick C, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer. 2013;119(2):363-370. doi:10.1002/cncr.27719.

285. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U S A. 1997;94(19):10367-10372. doi:10.1073/pnas.94.19.10367.

286. Alumkal JJ, Slottke R, Schwartzman J, Cherala G, Munar M, Graff JN, et al. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs. 2015;33(2):480-489. doi:10.1007/s10637-014-0189-z.

287. Atwell LL, Zhang Z, Mori M, Farris PE, Vetto JT, Naik AM, et al. Sulforaphane bioavailability and chemopreventive activity in women scheduled for breast biopsy. Cancer Prev Res (Phila). 2015;8(12):1184-1191. doi:10.1158/1940-6207.CAPR-15-0119.

288. Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, Chen JG, Chen TY, Fahey JW, Talalay P. Keap1-Nrf2 signaling: a target for cancer prevention by sulforaphane. Top Curr Chem. 2013;329:163-177. doi:10.1007/128_2012_339.

289. Cipolla BG, Mandron E, Lefort JM, Coadou MM, Flam T, Fofana M, et al. Effect of sulforaphane in men with prostate cancer: a randomized controlled trial. Cancer Prev Res (Phila). 2019;12(9):543-552.

290. Traka MH, Spinks CA, Dainty JR, Melchini A, Ball RY, Mills RD, et al. Treatment with sulforaphane-rich broccoli sprout extracts in men with biochemical recurrence after radical prostatectomy: a randomized, placebo-controlled trial. J Funct Foods. 2020;72:104047.

291. Ferry DR, Smith A, Malkhandi J, Fyfe DW, deTakats PG, Anderson D, et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and in vivo inhibition of protein tyrosine kinases. Clin Cancer Res. 1996;2(4):659-668.

292. Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol. 2012;83(1):6-15. doi:10.1016/j.bcp.2011.08.010.

293. Andres S, Pevny S, Ziegenhagen R, Bakhiya N, Schäfer B, Hirsch-Ernst KI, et al. Safety aspects of the use of quercetin as a dietary supplement. Mol Nutr Food Res. 2018;62(1):1700447.

294. Boots AW, Haenen GRMM, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;585(2-3):325-337. doi:10.1016/j.ejphar.2008.03.008.

295. Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010;70(22):9003-9011. doi:10.1158/0008-5472.CAN-10-2364.

296. Patel KR, Brown VA, Jones DJL, Britton RG, Hemingway D, Miller AS, et al. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res. 2010;70(19):7392-7399. doi:10.1158/0008-5472.CAN-10-2027.

297. Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, et al. Phase I randomized, double-blind pilot study of micronized resveratrol in patients with hepatic metastases. Cancer Prev Res (Phila). 2011;4(9):1419-1425. doi:10.1158/1940-6207.CAPR-11-0148.

298. Smoliga JM, Blanchard O. Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules. 2014;19(11):17154-17172. doi:10.3390/molecules191117154.

299. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44. doi:10.1056/NEJMoa1809944.

300. Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann Oncol. 2019;30(5):733-743. doi:10.1093/annonc/mdz059.

301. Chandler PD, Chen WY, Ajala ON, Hazra A, Cook N, Bubes V, et al. Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. JAMA Netw Open. 2020;3(11):e2025850.

302. Urashima M, Ohdaira H, Akutsu T, Okada S, Yoshida M, Kitajima M, et al. Effect of vitamin D supplementation on relapse-free survival among patients with digestive tract cancer: the AMATERASU randomized clinical trial. JAMA. 2019;321(14):1361-1369. doi:10.1001/jama.2019.2210.

303. Ng K, Nimeiri HS, McCleary NJ, Abrams TA, Yurgelun MB, Bullock AJ, et al. Effect of vitamin D3 supplementation on cancer survival in patients with metastatic colorectal cancer: the SUNSHINE randomized clinical trial. JAMA. 2019;321(14):1370-1379. doi:10.1001/jama.2019.2402.

304. Grant WB. Vitamin D: evidence-based health benefits and recommendations for population guidelines. Nutrients. 2025;17(2):278. doi:10.3390/nu17020278.

305. Lissoni P, Barni S, Mandalà M, Ardizzoia A, Paolorossi F, Vaghi M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumor patients with poor clinical status. Eur J Cancer. 1999;35(12):1688-1692.

306. Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005;39(4):360-366.

307. Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, et al. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012;11(4):293-303.

308. Sánchez-Barceló EJ, Mediavilla MD, Tan DX, Reiter RJ. Clinical uses of melatonin: evaluation of human trials. Curr Med Chem. 2010;17(19):2070-2095.

309. Seely D, Legacy M, Auer RC, Fazekas A, Delic E, Anstee C, et al. Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): a randomized placebo-controlled clinical trial. EClinicalMedicine. 2021;33:100763. doi:10.1016/j.eclinm.2021.100763.

310. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet. 1994;343(8906):1122-1126. doi:10.1016/S0140-6736(94)90233-X.

311. Oba K, Teramukai S, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer: a meta-analysis of randomized controlled trials. Cancer Immunol Immunother. 2007;56(6):905-911. doi:10.1007/s00262-006-0248-1.

312. Ina K, Kataoka T, Ando T. The use of lentinan for treating gastric cancer. Anticancer Agents Med Chem. 2013;13(5):681-688. doi:10.2174/1871520611313050002.

313. Ramberg JE, Nelson ED, Sinnott RA. Immunomodulatory dietary polysaccharides: a systematic review of the literature. Nutr J. 2010;9:54. doi:10.1186/1475-2891-9-54.

314. Fearon KCH, Barber MD, Moses AGW, Ahmedzai SH, Taylor GS, Tisdale MJ, et al. Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol. 2006;24(21):3401-3407. doi:10.1200/JCO.2005.04.5724.

315. Colomer R, Moreno-Nogueira JM, García-Luna PP, García-Peris P, García-de-Lorenzo A, Zarazaga A, et al. N-3 fatty acids, cancer and cachexia: a systematic review of the literature. Br J Nutr. 2007;97(5):823-831. doi:10.1017/S000711450765795X.

316. Mocellin MC, Camargo CQ, Nunes EA, Fiates GMR, Trindade EBSM. A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer. Clin Nutr. 2016;35(2):359-369. doi:10.1016/j.clnu.2015.04.013.

317. Murphy RA, Mourtzakis M, Chu QSC, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117(16):3774-3780. doi:10.1002/cncr.25933.

318. Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle TS, Lehr J, et al. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst. 1995;87(5):348-353. doi:10.1093/jnci/87.5.348.

319. Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI. Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer Prostatic Dis. 2003;6:301-304. doi:10.1038/sj.pcan.4500679.

320. Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009;344(14):1788-1791. doi:10.1016/j.carres.2008.08.038.

321. Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117(16):3788-3795. doi:10.1002/cncr.25945.

322. Ammon HPT. Boswellic acids in chronic inflammatory diseases. Planta Med. 2006;72(12):1100-1116. doi:10.1055/s-2006-947227.

323. Poeckel D, Werz O. Boswellic acids: biological actions and molecular targets. Curr Med Chem. 2006;13(28):3359-3369. doi:10.2174/092986706779010333.

324. Frank A, Unger M. Analysis of boswellic acids in Boswellia serrata by liquid chromatography: detection of β acid. J Chromatogr A. 2006; 1112:255-260.

325. Delia P, Sansotta G, Donato V, Frosina P, Messina G, De Renzis C, et al. Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol. 2007;13(6):912-915. doi:10.3748/wjg.v13.i6.912.

326. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-97. doi:10.1126/science.aan3706.

327. Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632-1640. doi:10.1126/science.aaz7015.

328. Derosa L, Hellmann MD, Spaziano M, Halpenny D, Fidelle M, Rizvi H, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29(6):1437-1444. doi:10.1093/annonc/mdy103.

329. Tröger W, Zdrale Z, Tisma N, MatijevićM. Five-year follow-up of patients with early stage breast cancer after a randomized, multicenter, comparative study of add-on Viscum album extracts. Evid Based Complement Alternat Med. 2012; 2012:219531. doi:10.1155/2012/219531.

330. Tröger W, Galun D, Reif M, Schumann A, StankovićN, MiliććM. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a prospective randomized controlled trial. Dtsch Arztebl Int. 2014;111(29-30):493-502. doi:10.3238/arztebl.2014.0493.

331. Loef M, Walach H. Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20:227. doi:10.1186/s12906-020-03013-3.

332. Kienle GS, Kiene H. Influence of Viscum album L extracts on quality of life in cancer patients: a systematic review of controlled clinical trials. Integr Cancer Ther. 2010;9(2):142-157. doi:10.1177/1534735410369673.

333. Ostermann T, Bussing A. Retrolective studies on the survival of cancer patients treated with mistletoe extracts: a meta-analysis. Explore (NY). 2012;8(5):277-281. doi:10.1016/j.explore.2012.06.005.

334. Tröger W, Stojanov J, Milenkovic A, et al. Mistletoe therapy in breast cancer patients: a randomized controlled trial. J Clin Oncol. 2010;28(15_suppl):e13000. Conference abstract; retain as an abstract rather than a full journal article.

335. Tröger W, Hamre H, Matthes B, et al. Mistletoe extract in metastatic colorectal cancer: a randomized controlled trial. Anticancer Res. 2008;28(5B):3193-3198.

336. Paller CJ, Wang L, Fu W, Kumar R, Durham JN, Azad NS, et al. Phase I trial of intravenous mistletoe extract in advanced cancer. Cancer Res Commun. 2023;3(2):338-346. doi:10.1158/2767-9764.CRC-23-0002.

337. Thronicke A, Lindner C, Schad F. Combined immune checkpoint blockade and Helixor therapy in oncology: real-world tolerability and subgroup survival. Int J Mol Sci. 2025;26(8):3669. doi:10.3390/ijms26083669.

338. Moertel CG, Fleming TR, Rubin J, Kvols LK, Sarna G, Koch R, et al. A clinical trial of amygdalin in the treatment of human cancer. N Engl J Med. 1982;306(4):201-206. doi:10.1056/NEJM198201283060403.

339. Milazzo S, Ernst E, Lejeune S, Horneber M. Laetrile treatment for cancer. Cochrane Database Syst Rev. 2015;(4):CD005476.

340. Bromley J, Hughes BG, Leong DC, Buckley NA. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother. 2005;39(9):1566-1569.

341. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.

342. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301(1):39-51.

343. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-1268.

344. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008;14(5-6):353-357.

345. Prasad AS. Zinc: an overview. Nutrition. 1995;11(1 Suppl):93-99.

346. Rock CL, Thomson CA, Sullivan KR, Howe CL, Kushi LH, Caan BJ, et al. American Cancer Society nutrition and physical activity guideline for cancer survivors. CA Cancer J Clin. 2022;72(3):230-262. doi:10.3322/caac.21719.

347. Schmitz KH, Campbell AM, Stuiver MM, Pinto BM, Schwartz AL, Morris GS, et al. Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA Cancer J Clin. 2019;69(6):468-484.

348. Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X, et al. Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol. 2015;33(10):1104-1111.

349. Ligibel JA, Bohlke K, May AM, Clinton SK, Demark-Wahnefried W, Gilchrist SC, et al. Exercise, diet, and weight management during cancer treatment: ASCO guideline. J Clin Oncol. 2022;40(22):2491-2507.

350. Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise guidelines for cancer survivors: consensus statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019;51(11):2375-2390.

351. National Academies of Sciences, Engineering, and Medicine. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington (DC): National Academies Press; 2013.

352. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. 2012;27(10):1361-1367.

353. Mao JJ, Ismaila N, Bao T, Barton D, Ben-Arye E, Garland EL, et al. Integrative medicine for pain management in oncology: Society for Integrative Oncology-ASCO guideline. J Clin Oncol. 2022;40(34):3998-4024.

354. Carlson LE, Ismaila N, Addington EL, Asher GN, Atreya C, Balneaves LG, et al. Integrative oncology care of symptoms of anxiety and depression in adults with cancer: Society for Integrative Oncology-ASCO guideline. J Clin Oncol. 2023;41(28):4562-4591.

355. Schilsky RL. Personalized medicine in oncology: the future is now. Nat Rev Drug Discov. 2010;9(5):363-366.

356. Rock CL, Thomson CA, Sullivan KR, Howe CL, Kushi LH, Caan BJ, et al. American Cancer Society nutrition and physical activity guideline for cancer survivors. CA Cancer J Clin. 2022;72(3):230-262.

357. Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5:66. doi:10.1038/s41572-019-0111-2.

358. Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. Lancet. 2021;397(10286):1750-1769.

359. Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(8):1194-1220. doi:10.1093/annonc/mdz173.

360. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663.

361. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628. doi:10.1056/NEJMoa1814017.

362. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690.

363. Dowsett M, Forbes JF, Bradley R, Ingle J, Aihara T, Bliss J, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341-1352.

364. Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, et al. Effect of metformin versus placebo on invasive disease-free survival in patients with breast cancer: the MA.32 randomized clinical trial. JAMA. 2022;327(20):1963-1973. doi:10.1001/jama.2022.6147.

365. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830.

366. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687-1717. doi:10.1016/S0140-6736(05)66544-0.

367. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398(10299):535-554.

368. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small-cell lung cancer. Nature. 2018;553(7689):446-454. doi:10.1038/nature25183.

369. The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543-550. doi:10.1038/nature13385.

370. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-957. doi:10.1056/NEJMoa0810699.

371. Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440.

372. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795.

373. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Cső T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774.

374. West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone in metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):924-937.

375. Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. doi:10.1001/jama.2014.3741.

376. Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29 Suppl 4:iv192-iv237. doi:10.1093/annonc/mdy275.

377. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467-1480. doi:10.1016/S0140-6736(19)32319-0.

378. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350-1356. doi:10.1038/nm.3967.

379. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-337. doi:10.1038/nature11252.

380. André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207-2218. doi:10.1056/NEJMoa2017699.

381. Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182-1191. doi:10.1016/S1470-2045(17)30422-9.

382. Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, et al. Encorafenib plus cetuximab and binimetinib for BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632-1643. doi:10.1056/NEJMoa1908075.

383. Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378(13):1177-1188. doi:10.1056/NEJMoa1713709.

384. Güller U, Hayoz S, Horber D, Jochum W, De Dosso S, Koeberle D, et al. Adjuvant aspirin treatment in PIK3CA-mutated colon cancer patients: the SAKK 41/13 prospective randomized placebo-controlled double-blind trial. Clin Cancer Res. 2025;31(15):3142-3149. doi:10.1158/1078-0432.CCR-24-4048.

385. Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395(10242):2008-2020. doi:10.1016/S0140-6736(20)30974-0.

386. Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, et al. Pancreatic cancer. Nat Rev Dis Primers. 2016;2:16022. doi:10.1038/nrdp.2016.22.

387. Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47-52. doi:10.1038/nature16965.

388. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. doi:10.1056/NEJMoa1011923.

389. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. doi:10.1056/NEJMoa1304369.

390. Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317-327. doi:10.1056/NEJMoa1903387.

391. Jameson GS, Borazanci E, Babiker HM, Villalobos VM, Anderson A, Khashab T, et al. Response rate following treatment with hydroxychloroquine in patients with advanced pancreatic cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2020;6(10):e202081.

392. Murphy JE, Wo JY, Ryan DP, Clark JW, Jiang W, Yeap BY, et al. Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5(7):1020-1027. doi:10.1001/jamaoncol.2019.0892.

393. Ramaswamy A, Bhargava P, Gota V, Srinivas S, Sultana N, Mandavkar S, et al. Efficacy of losartan plus modified FOLFIRINOX versus modified FOLFIRINOX in advanced pancreatic cancers: a randomized clinical trial (AFPAC Study). Cancer. 2025;131(13):e35945. doi:10.1002/cncr.35945.

394. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. doi:10.1038/s41572-020-00240-3.

395. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301-1314. doi:10.1016/S0140-6736(18)30010-2.

396. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450-1462. doi:10.1056/NEJMra1713263.

397. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-390. doi:10.1056/NEJMoa0708857.

398. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173. doi:10.1016/S0140-6736(18)30207-1.

399. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745.

400. Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, et al. Cabozantinib plus atezolizumab versus sorafenib for untreated advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(8):995-1008. doi:10.1016/S1470-2045(22)00370-6.

401. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado A, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681-693. doi:10.1016/j.jhep.2021.11.018.

402. Simon TG, Ma Y, Ludvigsson JF, Chong DQ, Giovannucci EL, Fuchs CS, et al. Association between aspirin use and risk of hepatocellular carcinoma. JAMA Oncol. 2018;4(12):1683-1690. doi:10.1001/jamaoncol.2018.2988.

403. Zhou YY, Zhu GQ, Wang Y, Zheng JN, Ruan LY, Cheng Z, et al. Systematic review with meta-analysis: statins and risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2016;44(9):971-979. doi:10.1111/apt.13792.

404. Smyth EC, Nilsson M, Grabsch HI, van Grieken NCT, Lordick F. Gastric cancer. Lancet. 2020;396(10251):635-648. doi:10.1016/S0140-6736(20)31288-5.

405. Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021;71(3):264-279. doi:10.3322/caac.21657.

406. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202-209. doi:10.1038/nature13480.

407. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-697. doi:10.1016/S0140-6736(10)61121-X.

408. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40. doi:10.1016/S0140-6736(21)00797-2.

409. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419-2430. doi:10.1056/NEJMoa2004413.

410. Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GLOW): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. doi:10.1016/S0140-6736(23)00620-7.

411. Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(9):2133-2141. doi:10.1038/s41591-023-02465-7.

412. Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology. 2016;150(5):1113-1124.e5. doi:10.1053/j.gastro.2016.01.028.

413. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240-1253. doi:10.1016/S0140-6736(18)32552-2.

414. Bowtell DD, Böhm S, Ahmed AA, Aspuria PJ, Bast RC Jr, Beral V, et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2015;15(11):668-679. doi:10.1038/nrc4019.

415. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-615. doi:10.1038/nature10166.

416. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858.

417. González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962.

418. Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361.

419. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(9):1274-1284. doi:10.1016/S1470-2045(17)30469-2.

420. Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169-182. doi:10.1016/S0140-6736(18)32470-X.

421. Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191-e203. doi:10.1016/S2214-109X(19)30482-6.

422. Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12-19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.

423. Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244-265. doi:10.1136/jcp.55.4.244.

424. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928-1943. doi:10.1056/NEJMoa061760.

425. Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734-743. doi:10.1056/NEJMoa1309748.

426. Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385(20):1856-1867. doi:10.1056/NEJMoa2112435.

427. Arbyn M, Xu L, Simoens C, Martin-Hirsch PPL. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;(5):CD009069. doi:10.1002/14651858.CD009069.pub3.

428. Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412-1428. doi:10.1016/S0140-6736(22)00323-3.

429. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-17. doi:10.1016/0090-8258(83)90111-7.

430. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73. doi:10.1038/nature12113.

431. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE, a molecular-based classification for endometrial carcinoma. Cancer. 2017;123(5):802-813. doi:10.1002/cncr.30444.

432. Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330.

433. Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158. doi:10.1056/NEJMoa2216334.

434. Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312.

435. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113(2):299-310. doi:10.1038/bjc.2015.190.

436. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783-2795. doi:10.1016/S0140-6736(16)30172-6.

437. Fagin JA, Wells SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375(11):1054-1067. doi:10.1056/NEJMra1501993.

438. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690. doi:10.1016/j.cell.2014.09.050.

439. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020.

440. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-328. doi:10.1016/S0140-6736(14)60421-9.

441. Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-630. doi:10.1056/NEJMoa1406470.

442. Wirth LJ, Durante C, Brose MS, Elisei R, Iñiguez-Ariza NM, Pak K, et al. Selpercatinib efficacy and safety in RET-altered thyroid cancers. N Engl J Med. 2020;383(9):825-835. doi:10.1056/NEJMoa2005651.

443. Bible KC, Kebebew E, Brierley J, Brito JP, Fagin JA, et al. 2021 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2021;31(3):337-386. doi:10.1089/thy.2020.0944.

444. Filetti S, Durante C, Hartl D, Leboulleux S, Locati LD, Newbold K, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1856-1883. doi:10.1093/annonc/mdz400.

445. Schadendorf D, van Akkooi ACJ, Berking C, Griewank KG, Gutzmer R, Hauschild A, et al. Melanoma. Lancet. 2018;392(10151):971-984. doi:10.1016/S0140-6736(18)31559-9.

446. Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell. 2015;161(7):1681-1696. doi:10.1016/j.cell.2015.05.044.

447. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-954. doi:10.1038/nature00766.

448. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. doi:10.1056/NEJMoa1003466.

449. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320-330. doi:10.1056/NEJMoa1412082.

450. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34. doi:10.1056/NEJMoa1504030.

451. Long GV, Stroyakovskiy D, Gogas H, Mandala M, Devereux S, de Braud F, et al. Dabrafenib and trametinib versus dabrafenib and placebo in patients with BRAF V600-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. N Engl J Med. 2014;371(20):1877-1888. doi:10.1056/NEJMoa1307534.

452. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Lao CD, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345-1356. doi:10.1056/NEJMoa1709684.

453. Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutierrez E, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24-34. doi:10.1056/NEJMoa2109970.

454. Amaral T, Ottaviano M, Arance A, Blank C, Chiarion-Sileni V, Donia M, et al. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025;36(1):10-30.

455. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nat Rev Dis Primers. 2017;3:17009. doi:10.1038/nrdp.2017.9.

456. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43-49. doi:10.1038/nature12222.

457. Linehan WM, Ricketts CJ. The cancer genome atlas of renal cell carcinoma: findings and clinical implications. Nat Rev Urol. 2019;16(9):539-552. doi:10.1038/s41585-019-0211-5.

458. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-1813. doi:10.1056/NEJMoa1510665.

459. Motzer RJ, Tannir NM, McDermott DF, Frontera OA, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126.

460. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714.

461. Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982.

462. Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716.

463. Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391.

464. Powles T, Albiges L, Bex A, Comperat E, Grünwald V, Kanesvaran R, et al. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(8):692-706.

465. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6:92. doi:10.1038/s41572-020-00224-3.

466. Leemans CR, Snijders PJF, Brakenhoff RH. The molecular landscape of head and neck cancer. Nat Rev Cancer. 2018;18(5):269-282. doi:10.1038/nrc.2018.11.

467. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217.

468. Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-582. doi:10.1038/nature14129.

469. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-1127. doi:10.1056/NEJMoa0802656.

470. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252.

471. Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7.

472. Gillison ML, Trotti AM, Harris J, Eisbruch A, Haraf DJ, Adelstein DJ, et al. Radiotherapy plus cetuximab or cisplatin for human papillomavirus-positive oropharyngeal cancer. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X.

473. Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral cavity, lip, and oropharynx: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1462-1475. doi:10.1016/j.annonc.2020.07.010.

474. Wen PY, Weller M, Lee EQ, Alexander BM, Barnholtz-Sloan JS, Barthel FP, et al. Glioblastoma in adults: a Society for Neuro-Oncology and EANO consensus review on current management and future directions. Neuro Oncol. 2020;22(8):1073-1113. doi:10.1093/neuonc/noaa106.

475. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. doi:10.1056/NEJMoa043330.

476. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. doi:10.1056/NEJMoa043331.

477. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-1068. doi:10.1038/nature07385.

478. Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110. doi:10.1016/j.ccr.2009.12.020.

479. Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, et al. Effect of tumor-treating fields plus maintenance temozolomide vs temozolomide alone on survival in glioblastoma. JAMA. 2017;318(23):2306-2316. doi:10.1001/jama.2017.18718.

480. Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170-186. doi:10.1038/s41571-020-00447-z.

481. Capper D, Reifenberger G, French P, Schweizer L, Weller M, Touat M, et al. EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro Oncol. 2023;25(5):813-826. doi:10.1093/neuonc/noad011.

482. Wick W, Gorlia T, Bendszus M, Taphoorn MJB, Sahm F, Harting I, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377(20):1954-1963. doi:10.1056/NEJMoa1707358.

483. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733-4740. doi:10.1200/JCO.2008.19.8721.

484. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867.

485. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy, and monitoring. Am J Hematol. 2020;95(6):691-709. doi:10.1002/ajh.25792.

486. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408-2417. doi:10.1056/NEJMoa062867.

487. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. doi:10.1182/blood-2017-09-806398.

488. Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235-242. doi:10.1056/NEJMoa011795.

489. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-3068. doi:10.1200/JCO.2013.54.8800.

490. Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99(9):1802-1824. doi:10.1002/ajh.27409.

491. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-448. doi:10.1056/NEJMoa1709866.

492. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447.

493. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56. doi:10.1056/NEJMoa1804980.

494. Casali PG, Abecassis N, Aro HT, Bauer S, Biagini R, Bielack S, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(11):1348-1365. doi:10.1016/j.annonc.2021.07.006.

495. Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M. Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer. 2011;11(8):541-557. doi:10.1038/nrc3087.

496. Cancer Genome Atlas Research Network. Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. Cell. 2017;171(4):950-965.e28. doi:10.1016/j.cell.2017.10.014.

497. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415-423. doi:10.1016/S1470-2045(14)70063-4.

498. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472-480. doi:10.1056/NEJMoa020461.

499. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of advanced soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488-497.

500. Gaspar N, Hawkins DS, Dirksen U, Lewis IJ, Ferrari S, Le Deley MC, et al. Ewing sarcoma: current management and future approaches. J Clin Oncol. 2015;33(27):3031-3039. doi:10.1200/JCO.2014.59.4890.

501. Bielack SS, Carrle D, Hardes J. Bone tumors in adolescents and young adults. Curr Treat Options Oncol. 2008;9(1):67-80. doi:10.1007/s11864-008-0057-6.

502. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379(9824):1428-1435. doi:10.1016/S0140-6736(11)61178-1.

503. Varadhachary GR, Raber MN. Cancer of unknown primary site. N Engl J Med. 2014;371(8):757-765. doi:10.1056/NEJMra1303917.

504. Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G; ESMO Guidelines Committee. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26 Suppl 5:v133-v138. doi:10.1093/annonc/mdv305.

505. Ross JS, Wang K, Gay L, Otto GA, White E, Iwanik K, et al. Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies. JAMA Oncol. 2015;1(1):40-49. doi:10.1001/jamaoncol.2014.216.

506. Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, Greco FA. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon Research Institute. J Clin Oncol. 2013;31(2):217-223. doi:10.1200/JCO.2012.43.3755.

507. Ross JS, Sokol ES, Moch H, Mileshkin L, Baciarello G, Losa F, et al. Comprehensive genomic profiling of carcinoma of unknown primary origin: retrospective molecular classification considering the CUPISCO study design. Oncologist. 2021;26(3):e394-e402. doi:10.1002/onco.13597.

508. Krämer A, Bochtler T, Pauli C, Shiu KK, Cook N, Janoski de Menezes J, et al. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024;404(10452):527-539. doi:10.1016/S0140-6736(24)00814-6.

509. Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, et al. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group study. J Clin Oncol. 2000;18(17):3101-3107.

510. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060-1072. doi:10.1016/j.cell.2012.03.042.

511. Stockwell BR, Angeli JPF, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273-285. doi:10.1016/j.cell.2017.09.021.

512. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22(4):266-282. doi:10.1038/s41580-020-00324-8.

513. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. doi:10.1126/science.aan4236.

514. Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602-609. doi:10.1126/science.abb5920.

515. Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018;18(7):407-418. doi:10.1038/s41568-018-0007-6.

516. Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018;359(6378):920-926. doi:10.1126/science.aao2774.

517. Pauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 2017;7(5):462-477. doi:10.1158/2159-8290.CD-16-1154.

518. Mateo J, Steuten L, Aftimos P, André F, Davies M, Garralda E, et al. Delivering precision oncology to patients with cancer. Nat Med. 2022;28(4):658-665. doi:10.1038/s41591-022-01717-2.

519. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-1517. doi:10.1056/NEJMoa1407222.

520. Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58. doi:10.1038/nrd.2018.168.

521. Dagogo-Jack I, Shaw AT. Tumor heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81-94. doi:10.1038/nrclinonc.2017.166.