REFERENCES

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-49.

2. Wild CP, Weiderpass E, Stewart BW. World Cancer Report: cancer research for cancer prevention. Available from: https://publications.iarc.fr/586. [Last accessed on 26 May 2025].

3. Joko-Fru WY, Miranda-Filho A, Soerjomataram I, et al. Breast cancer survival in sub-Saharan Africa by age, stage at diagnosis and human development index: a population-based registry study. Int J Cancer. 2020;146:1208-18.

4. Prager GW, Braga S, Bystricky B, et al. Global cancer control: responding to the growing burden, rising costs and inequalities in access. ESMO Open. 2018;3:e000285.

5. Zhong L, Li Y, Xiong L, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:201.

6. Housman G, Byler S, Heerboth S, et al. Drug resistance in cancer: an overview. Cancers. 2014;6:1769-92.

7. Luqmani YA. Mechanisms of drug resistance in cancer chemotherapy. Med Princ Pract. 2005;14 Suppl 1:35-48.

8. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805:105-17.

9. Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer. 2021;127:3029-30.

10. Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004;4:937-47.

11. Kovalski JR, Bhaduri A, Zehnder AM, et al. The functional proximal proteome of oncogenic ras includes mTORC2. Mol Cell. 2019;73:830-44.e12.

12. Rizos H, Menzies AM, Pupo GM, et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014;20:1965-77.

13. Montagut C, Sharma SV, Shioda T, et al. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 2008;68:4853-61.

14. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468:968-72.

15. Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun. 2012;3:724.

16. Corcoran RB, Dias-Santagata D, Bergethon K, Iafrate AJ, Settleman J, Engelman JA. BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci Signal. 2010;3:ra84.

17. Ligresti G, Militello L, Steelman LS, et al. PIK3CA mutations in human solid tumors: role in sensitivity to various therapeutic approaches. Cell Cycle. 2009;8:1352-8.

18. Manning BD, Toker A. AKT/PKB signaling: navigating the network. Cell. 2017;169:381-405.

19. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170:605-35.

20. Candido S, Salemi R, Piccinin S, Falzone L, Libra M. The PIK3CA H1047R mutation confers resistance to BRAF and MEK inhibitors in A375 melanoma cells through the cross-activation of MAPK and PI3K-Akt pathways. Pharmaceutics. 2022;14:590.

21. Shi H, Hugo W, Kong X, et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 2014;4:80-93.

22. Muñoz-Couselo E, Adelantado EZ, Ortiz C, García JS, Perez-Garcia J. NRAS-mutant melanoma: current challenges and future prospect. Onco Targets Ther. 2017;10:3941-7.

23. Hodis E, Watson IR, Kryukov GV, et al. A landscape of driver mutations in melanoma. Cell. 2012;150:251-63.

24. Mandalà M, Merelli B, Massi D. Nras in melanoma: targeting the undruggable target. Crit Rev Oncol Hematol. 2014;92:107-22.

25. Abel EV, Basile KJ, Kugel CH 3rd, et al. Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest. 2013;123:2155-68.

26. Kun E, Tsang YTM, Ng CW, Gershenson DM, Wong KK. MEK inhibitor resistance mechanisms and recent developments in combination trials. Cancer Treat Rev. 2021;92:102137.

27. Wagle N, Van Allen EM, Treacy DJ, et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 2014;4:61-8.

28. Oda K, Matsuoka Y, Funahashi A, Kitano H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005;1:2005.0010.

29. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283-96.

30. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159-69.

31. Gallagher EJ, LeRoith D. The proliferating role of insulin and insulin-like growth factors in cancer. Trends Endocrinol Metab. 2010;21:610-8.

32. Zhao S, Xue H, Hao CL, Jiang HM, Zheng HC. BTG1 overexpression might promote invasion and metastasis of colorectal cancer via decreasing adhesion and inducing epithelial-mesenchymal transition. Front Oncol. 2020;10:598192.

33. Correia AL, Bissell MJ. The tumor microenvironment is a dominant force in multidrug resistance. Drug Resist Updat. 2012;15:39-49.

34. Son B, Lee S, Youn H, Kim E, Kim W, Youn B. The role of tumor microenvironment in therapeutic resistance. Oncotarget. 2017;8:3933-45.

35. Ge R, Wang Z, Cheng L. Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance. NPJ Precis Oncol. 2022;6:31.

36. Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618-31.

37. Santoni M, Massari F, Amantini C, et al. Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother. 2013;62:1757-68.

38. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704-15.

39. Kuburich NA, Sabapathy T, Demestichas BR, Maddela JJ, den Hollander P, Mani SA. Proactive and reactive roles of TGF-β in cancer. Semin Cancer Biol. 2023;95:120-39.

40. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253-68.

41. Beury DW, Parker KH, Nyandjo M, Sinha P, Carter KA, Ostrand-Rosenberg S. Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors. J Leukoc Biol. 2014;96:1109-18.

42. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers. 2015;7:2443-58.

43. Kaur A, Webster MR, Marchbank K, et al. sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. Nature. 2016;532:250-4.

44. Wu F, Yang J, Liu J, et al. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther. 2021;6:218.

45. Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015;15:25-41.

46. Paraiso KH, Smalley KS. Fibroblast-mediated drug resistance in cancer. Biochem Pharmacol. 2013;85:1033-41.

47. Xavier CPR, Caires HR, Barbosa MAG, Bergantim R, Guimarães JE, Vasconcelos MH. The role of extracellular vesicles in the hallmarks of cancer and drug resistance. Cells. 2020;9:1141.

48. Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell. 2016;30:836-48.

49. Maleki S, Jabalee J, Garnis C. The role of extracellular vesicles in mediating resistance to anticancer therapies. Int J Mol Sci. 2021;22:4166.

50. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.

51. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290-3.

52. Deininger MW, Shah NP, Altman JK, et al. Chronic myeloid leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18:1385-415.

53. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966-84.

54. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200-28.

55. Berman E. How I treat chronic-phase chronic myelogenous leukemia. Blood. 2022;139:3138-47.

56. Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34:2851-7.

57. Radich JP, Deininger M, Abboud CN, et al. Chronic myeloid leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16:1108-35.

58. Hughes T, Saglio G, Branford S, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009;27:4204-10.

59. Mead AJ. Single cell genomics in chronic myeloid leukemia. HemaSphere. 2018;2:54-5.

60. Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017;543:733-7.

61. Neviani P, Harb JG, Oaks JJ, et al. PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells. J Clin Invest. 2013;123:4144-57.

62. Ma L, Shan Y, Bai R, et al. A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Sci Transl Med. 2014;6:252ra121.

63. Mitchell R, Hopcroft LEM, Baquero P, et al. Targeting BCR-ABL-independent TKI resistance in chronic myeloid leukemia by mTOR and autophagy inhibition. J Natl Cancer Inst. 2018;110:467-78.

64. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7:e577.

65. Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446:758-64.

66. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100:1965-71.

67. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-42.

68. Jones CL, Gearheart CM, Fosmire S, et al. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia. Blood. 2015;126:2202-12.

69. Verrills NM, Walsh BJ, Cobon GS, Hains PG, Kavallaris M. Proteome analysis of vinca alkaloid response and resistance in acute lymphoblastic leukemia reveals novel cytoskeletal alterations. J Biol Chem. 2003;278:45082-93.

70. Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023;10:E24-34.

71. Cortes JE, Kim DW, Pinilla-Ibarz J, et al; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369:1783-96.

72. Lipton JH, Chuah C, Guerci-Bresler A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612-21.

73. Alves R, Gonçalves AC, Rutella S, et al. Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia - from molecular mechanisms to clinical relevance. Cancers. 2021;13:4820.

74. Advani AS, Forman SJ, Rowe JM. The role of ponatinib in Ph+ ALL: new strategies and future directions. Blood Adv. 2023;7:2412-21.

75. Rousselot P, Coudé MM, Gokbuget N. Combining ponatinib with blinatumomab: a chemotherapy-free strategy for Ph+ ALL. Haematologica. 2022;107:1394-403.

76. Cerovska E, Salek C, Kundrat D, et al. ABC transporters are predictors of treatment failure in acute myeloid leukaemia. Biomed Pharmacother. 2024;170:115930.

77. van Galen JC, Kuiper RP, van Emst L, et al. BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia. Blood. 2010;115:4810-9.

78. Hogan LE, Meyer JA, Yang J, et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood. 2011;118:5218-26.

79. Nokin MJ, Ambrogio C, Nadal E, Santamaria D. Targeting infrequent driver alterations in non-small cell lung cancer. Trends Cancer. 2021;7:410-29.

80. Chevallier M, Borgeaud M, Addeo A, Friedlaender A. Oncogenic driver mutations in non-small cell lung cancer: past, present and future. World J Clin Oncol. 2021;12:217-37.

81. Johnson M, Garassino MC, Mok T, Mitsudomi T. Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: focus on novel therapies. Lung Cancer. 2022;170:41-51.

82. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4:1046-61.

83. Choi YL, Soda M, Yamashita Y, et al; ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363:1734-9.

84. Yang H, Wen L, Zhao C, et al. EGFR amplification is a putative resistance mechanism for NSCLC-LM patients with TKI therapy and is associated with poor outcome. Front Oncol. 2022;12:902664.

85. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4:120ra17.

86. Turke AB, Zejnullahu K, Wu YL, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010;17:77-88.

87. Sethy C, Kundu CN. 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition. Biomed Pharmacother. 2021;137:111285.

88. Das D, Preet R, Mohapatra P, et al. 5-Fluorouracil mediated anti-cancer activity in colon cancer cells is through the induction of Adenomatous Polyposis Coli: implication of the long-patch base excision repair pathway. DNA Repair. 2014;24:15-25.

89. Toriumi F, Kubota T, Saikawa Y, et al. Thymidylate synthetase (TS) genotype and TS/dihydropyrimidine dehydrogenase mRNA level as an indicator in determining chemosensitivity to 5-fluorouracil in advanced gastric carcinoma. Anticancer Res. 2004;24:2455-63.

90. Peters GJ, Backus HH, Freemantle S, et al. Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta. 2002;1587:194-205.

91. Verma H, Doshi J, Narendra G, Raju B, Singh PK, Silakari O. Energy decomposition and waterswapping analysis to investigate the SNP associated DPD mediated 5-FU resistance. SAR QSAR Environ Res. 2023;34:39-64.

92. Verma H, Narendra G, Raju B, Singh PK, Silakari O. Dihydropyrimidine dehydrogenase-mediated resistance to 5-fluorouracil: mechanistic investigation and solution. ACS Pharmacol Transl Sci. 2022;5:1017-33.

93. Wang WB, Yang Y, Zhao YP, Zhang TP, Liao Q, Shu H. Recent studies of 5-fluorouracil resistance in pancreatic cancer. World J Gastroenterol. 2014;20:15682-90.

94. He L, Zhu H, Zhou S, et al. Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells. Exp Mol Med. 2018;50:1-12.

95. Shi Z, Yu X, Yuan M, et al. Activation of the PERK-ATF4 pathway promotes chemo-resistance in colon cancer cells. Sci Rep. 2019;9:3210.

96. Dong S, Liang S, Cheng Z, et al. ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer. J Exp Clin Cancer Res. 2022;41:15.

97. Long S, Wang J, Weng F, et al. ECM1 regulates the resistance of colorectal cancer to 5-FU treatment by modulating apoptotic cell death and epithelial-mesenchymal transition induction. Front Pharmacol. 2022;13:1005915.

98. Ghosh S, Singh R, Vanwinkle ZM, et al. Microbial metabolite restricts 5-fluorouracil-resistant colonic tumor progression by sensitizing drug transporters via regulation of FOXO3-FOXM1 axis. Theranostics. 2022;12:5574-95.

99. Escalante PI, Quiñones LA, Contreras HR. Epithelial-mesenchymal transition and microRNAs in colorectal cancer chemoresistance to FOLFOX. Pharmaceutics. 2021;13:75.

100. Kim BH, Kwon J, Kim K. Evaluation of the benefit of radiotherapy in patients with occult breast cancer: a population-based analysis of the SEER database. Cancer Res Treat. 2018;50:551-61.

101. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127-37.

102. Martínez-Sáez O, Prat A. Current and future management of HER2-positive metastatic breast cancer. JCO Oncol Pract. 2021;17:594-604.

103. Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog. 2012;17:1-16.

104. Patel A, Unni N, Peng Y. The changing paradigm for the treatment of HER2-positive breast cancer. Cancers. 2020;12:2081.

105. Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: advances and future directions. Nat Rev Drug Discov. 2023;22:101-26.

106. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-92.

107. Rimawi MF, Schiff R, Osborne CK. Targeting HER2 for the treatment of breast cancer. Annu Rev Med. 2015;66:111-28.

108. Vivekanandhan S, Knutson KL. Resistance to trastuzumab. Cancers. 2022;14:5115.

109. Greenblatt K, Khaddour K. Trastuzumab. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532246/. [Last accessed on 26 May 2025].

110. Arribas J, Baselga J, Pedersen K, Parra-Palau JL. p95HER2 and breast cancer. Cancer Res. 2011;71:1515-9.

111. Scaltriti M, Rojo F, Ocaña A, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99:628-38.

112. Miricescu D, Totan A, Stanescu-Spinu II, Badoiu SC, Stefani C, Greabu M. PI3K/AKT/mTOR signaling pathway in breast cancer: from molecular landscape to clinical aspects. Int J Mol Sci. 2020;22:173.

113. Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res. 2009;15:7479-91.

114. Dave A, Hernández ML, He Z, et al. 12-oxo-phytodienoic acid accumulation during seed development represses seed germination in Arabidopsis. Plant Cell. 2011;23:583-99.

115. Jensen MB, Ejlertsen B, Mouridsen HT, Christiansen P; Danish Breast Cancer Cooperative Group. Improvements in breast cancer survival between 1995 and 2012 in Denmark: the importance of earlier diagnosis and adjuvant treatment. Acta Oncol. 2016;55 Suppl 2:24-35.

116. Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117-27.

117. Elshazly AM, Gewirtz DA. An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer. Cancer Drug Resist. 2022;5:472-86.

118. Berns K, Horlings HM, Hennessy BT, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12:395-402.

119. Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3:317-30.

120. Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011;29:4452-61.

121. Bosch A, Li Z, Bergamaschi A, et al. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med. 2015;7:283ra51.

122. Juric D, Janku F, Rodón J, et al. Alpelisib plus fulvestrant in PIK3CA-altered and PIK3CA-wild-type estrogen receptor-positive advanced breast cancer: a phase 1b clinical trial. JAMA Oncol. 2019;5:e184475.

123. Freedland SJ, Davis M, Epstein AJ, Arondekar B, Ivanova JI. Real-world treatment patterns and overall survival among men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the US Medicare population. Prostate Cancer Prostatic Dis. 2024;27:327-33.

124. Rebello RJ, Oing C, Knudsen KE, et al. Prostate cancer. Nat Rev Dis Primers. 2021;7:9.

125. Gao X. Targeting androgen receptor mutations in metastatic castration-resistant prostate cancer with a novel androgen biosynthesis inhibitor. NEJM Evid. 2024;3:EVIDe2300298.

126. Goncharov AP, Vashakidze N, Kharaishvili G. Epithelial-mesenchymal transition: a fundamental cellular and microenvironmental process in benign and malignant prostate pathologies. Biomedicines. 2024;12:418.

127. Li X, Xiong H, Mou X, et al. Androgen receptor cofactors: a potential role in understanding prostate cancer. Biomed Pharmacother. 2024;173:116338.

128. Zengin ZB, Henderson NC, Park JJ, et al. Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration. Prostate Cancer Prostatic Dis. 2024.

129. Wang L, Williamson SR, Zhang S, et al. Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma. Mol Carcinog. 2015;54:900-7.

130. Helminen L, Huttunen J, Tulonen M, et al. Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer. Nucleic Acids Res. 2024;52:625-42.

131. Quigley DA, Dang HX, Zhao SG, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. 2018;174:758-69.e9.

132. Van-Duyne G, Blair IA, Sprenger C, Moiseenkova-Bell V, Plymate S, Penning TM. The androgen receptor. Vitam Horm 2023;123:439-81.

133. Saranyutanon S, Srivastava SK, Pai S, Singh S, Singh AP. Therapies targeted to androgen receptor signaling axis in prostate cancer: progress, challenges, and hope. Cancers. 2019;12:51.

134. Le TK, Duong QH, Baylot V, et al. Castration-resistant prostate cancer: from uncovered resistance mechanisms to current treatments. Cancers. 2023;15:5047.

135. Sun R, Yan B, Li H, et al. Androgen receptor variants confer castration resistance in prostate cancer by counteracting antiandrogen-induced ferroptosis. Cancer Res. 2023;83:3192-204.

136. Tilki D, Schaeffer EM, Evans CP. Understanding mechanisms of resistance in metastatic castration-resistant prostate cancer: the role of the androgen receptor. Eur Urol Focus. 2016;2:499-505.

137. Li Y, Chan SC, Brand LJ, Hwang TH, Silverstein KA, Dehm SM. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res. 2013;73:483-9.

138. Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013;32:5501-11.

139. Khan A, Mao Y, Tahreem S, Wei DQ, Wang Y. Structural and molecular insights into the mechanism of resistance to enzalutamide by the clinical mutants in androgen receptor (AR) in castration-resistant prostate cancer (CRPC) patients. Int J Biol Macromol. 2022;218:856-65.

140. Daniels VA, Luo J, Paller CJ, Kanayama M. Therapeutic approaches to targeting androgen receptor splice variants. Cells. 2024;13:104.

141. Bailey P, Chang DK, Nones K, et al; Australian Pancreatic Cancer Genome Initiative. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016;531:47-52.

142. Luo J. KRAS mutation in pancreatic cancer. Semin Oncol. 2021;48:10-8.

143. Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021;6:386.

144. Gu M, Gao Y, Chang P. KRAS mutation dictates the cancer immune environment in pancreatic ductal adenocarcinoma and other adenocarcinomas. Cancers. 2021;13:2429.

145. Genovese G, Carugo A, Tepper J, et al. Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer. Nature. 2017;542:362-6.

146. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371:1039-49.

147. Pratilas CA, Solit DB. Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res. 2010;16:3329-34.

148. Kandalaft LE, Dangaj Laniti D, Coukos G. Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation. Nat Rev Cancer. 2022;22:640-56.

149. Veneziani AC, Gonzalez-Ochoa E, Alqaisi H, et al. Heterogeneity and treatment landscape of ovarian carcinoma. Nat Rev Clin Oncol. 2023;20:820-42.

150. Havasi A, Cainap SS, Havasi AT, Cainap C. Ovarian cancer-insights into platinum resistance and overcoming it. Medicina. 2023;59:544.

151. Webb PM, Jordan SJ. Global epidemiology of epithelial ovarian cancer. Nat Rev Clin Oncol. 2024;21:389-400.

152. McCluggage WG, Singh N, Gilks CB. Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020). Histopathology. 2022;80:762-78.

153. Shih IM, Wang Y, Wang TL. The origin of ovarian cancer species and precancerous landscape. Am J Pathol. 2021;191:26-39.

154. Mitri Z, Goodyear SM, Mills G. Strategies for the prevention or reversal of PARP inhibitor resistance. Expert Rev Anticancer Ther. 2024;24:959-75.

155. Prados-Carvajal R, Irving E, Lukashchuk N, Forment JV. Preventing and overcoming resistance to PARP inhibitors: a focus on the clinical landscape. Cancers. 2021;14:44.

156. Dias MP, Moser SC, Ganesan S, Jonkers J. Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nat Rev Clin Oncol. 2021;18:773-91.

157. Bhamidipati D, Haro-Silerio JI, Yap TA, Ngoi N. PARP inhibitors: enhancing efficacy through rational combinations. Br J Cancer. 2023;129:904-16.

158. Gourley C, Balmaña J, Ledermann JA, et al. Moving from poly (ADP-ribose) polymerase inhibition to targeting DNA repair and DNA damage response in cancer therapy. J Clin Oncol. 2019;37:2257-69.

159. Klotz DM, Wimberger P. Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies? Arch Gynecol Obstet. 2020;302:1087-102.

160. Topatana W, Juengpanich S, Li S, et al. Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation. J Hematol Oncol. 2020;13:118.

161. Miller RE, El-Shakankery KH, Lee JY. PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies. J Gynecol Oncol. 2022;33:e44.

162. Alatise KL, Gardner S, Alexander-Bryant A. Mechanisms of drug resistance in ovarian cancer and associated gene targets. Cancers. 2022;14:6246.

163. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11:1156-66.

164. Gallyas F Jr, Sumegi B, Szabo C. Role of Akt activation in PARP inhibitor resistance in cancer. Cancers. 2020;12:532.

165. Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol. 2018;15:273-91.

166. Bedard PL, Tabernero J, Janku F, et al. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res. 2015;21:730-8.

167. Farley J, Brady WE, Vathipadiekal V, et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 2013;14:134-40.

168. Soberanis Pina P, Lheureux S. Overcoming PARP inhibitor resistance in ovarian cancer. Int J Gynecol Cancer. 2023;33:364-76.

169. Ang JE, Gourley C, Powell CB, et al. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013;19:5485-93.

170. Cecere SC, Giannone G, Salutari V, et al. Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: real world data and post progression outcome. Gynecol Oncol. 2020;156:38-44.

171. Ngoi NY, Sundararajan V, Tan DS. Exploiting replicative stress in gynecological cancers as a therapeutic strategy. Int J Gynecol Cancer. 2020;30:1224-38.

172. Wethington SL, Shah PD, Martin L, et al. Combination ATR (ceralasertib) and PARP (olaparib) inhibitor (CAPRI) trial in acquired PARP inhibitor-resistant homologous recombination-deficient ovarian cancer. Clin Cancer Res. 2023;29:2800-7.

173. Konstantinopoulos PA, Cheng SC, Wahner Hendrickson AE, et al. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21:957-68.

174. Westin SN, Labrie M, Litton JK, et al. Phase Ib dose expansion and translational analyses of olaparib in combination with capivasertib in recurrent endometrial, triple-negative breast, and ovarian cancer. Clin Cancer Res. 2021;27:6354-65.

175. Yap TA, Kristeleit R, Michalarea V, et al. Phase I trial of the PARP inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2- and non-BRCA1/2-mutant cancers. Cancer Discov. 2020;10:1528-43.

176. Cristea MC, Stewart D, Synold T, et al. A phase I study of Mirvetuximab Soravtansine and gemcitabine in patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, or endometrial cancer, or triple negative breast cancer. Gynecol Oncol. 2024;182:124-31.

177. Zhou J, Gelot C, Pantelidou C, et al. A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors. Nat Cancer. 2021;2:598-610.

178. Zatreanu D, Robinson HMR, Alkhatib O, et al. Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance. Nat Commun. 2021;12:3636.

179. Zhang M, Wang J, Guo Y, Yue H, Zhang L. Activation of PI3K/AKT/mTOR signaling axis by UBE2S inhibits autophagy leading to cisplatin resistance in ovarian cancer. J Ovarian Res. 2023;16:240.

180. Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma multiforme: a review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 2017;18:3-9.

181. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16:1-13.

182. Cheng L, Huang Z, Zhou W, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153:139-52.

183. Ueda K, Cornwell MM, Gottesman MM, et al. The mdr1 gene, responsible for multidrug-resistance, codes for P-glycoprotein. Biochem Biophys Res Commun. 1986;141:956-62.

184. Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258:1650-4.

185. Tsuji A, Terasaki T, Takabatake Y, et al. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 1992;51:1427-37.

186. Desjardins A, Gromeier M, Herndon JE 2nd, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150-61.

187. Chen KT, Lin YJ, Chai WY, et al. Neuronavigation-guided focused ultrasound (NaviFUS) for transcranial blood-brain barrier opening in recurrent glioblastoma patients: clinical trial protocol. Ann Transl Med. 2020;8:673.

188. Thomas E, Colombeau L, Gries M, et al. Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma. Int J Nanomedicine. 2017;12:7075-88.

189. Pandey V, Haider T, Chandak AR, Chakraborty A, Banerjee S, Soni V. Surface modified silk fibroin nanoparticles for improved delivery of doxorubicin: development, characterization, in-vitro studies. Int J Biol Macromol. 2020;164:2018-27.

190. Yang Z, Wei D, Dai X, et al. C8-substituted imidazotetrazine analogs overcome temozolomide resistance by inducing DNA adducts and DNA damage. Front Oncol. 2019;9:485.

191. Thon N, Kreth S, Kreth FW. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. Onco Targets Ther. 2013;6:1363-72.

192. Cabrini G, Fabbri E, Lo Nigro C, Dechecchi MC, Gambari R. Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review). Int J Oncol. 2015;47:417-28.

193. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061-8.

194. Weller M, Butowski N, Tran DD, et al; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18:1373-85.

195. Hasselbalch B, Lassen U, Hansen S, et al. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. Neuro Oncol. 2010;12:508-16.

196. Schreck KC, Grossman SA, Pratilas CA. BRAF mutations and the utility of RAF and MEK inhibitors in primary brain tumors. Cancers. 2019;11:1262.

197. Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (Temodar). AJNR Am J Neuroradiol. 2010;31:1383-4.

198. Verbeek B, Southgate TD, Gilham DE, Margison GP. O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy. Br Med Bull. 2008;85:17-33.

199. Erasimus H, Gobin M, Niclou S, Van Dyck E. DNA repair mechanisms and their clinical impact in glioblastoma. Mutat Res Rev Mutat Res. 2016;769:19-35.

200. Stritzelberger J, Distel L, Buslei R, Fietkau R, Putz F. Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine. Clin Transl Oncol. 2018;20:508-16.

201. Fujii S, Sobol RW, Fuchs RP. Double-strand breaks: when DNA repair events accidentally meet. DNA Repair. 2022;112:103303.

202. Dirkse A, Golebiewska A, Buder T, et al. Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. Nat Commun. 2019;10:1787.

203. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396-401.

204. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756-60.

205. Uribe D, Torres Á, Rocha JD, et al. Multidrug resistance in glioblastoma stem-like cells: role of the hypoxic microenvironment and adenosine signaling. Mol Aspects Med. 2017;55:140-51.

206. Westover D, Li F. New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies. J Exp Clin Cancer Res. 2015;34:159.

207. Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal. 2014;21:1516-54.

208. Monteiro AR, Hill R, Pilkington GJ, Madureira PA. The role of hypoxia in glioblastoma invasion. Cells. 2017;6:45.

209. Hu YL, DeLay M, Jahangiri A, et al. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res. 2012;72:1773-83.

210. Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2006;144:337-43.

211. Nijman SM. Synthetic lethality: general principles, utility and detection using genetic screens in human cells. FEBS Lett. 2011;585:1-6.

212. Sudo M, Mori S, Madan V, Yang H, Leong G, Koeffler HP. Short-hairpin RNA library: identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer. Oncotarget. 2015;6:814-24.

213. Blakely CM, Pazarentzos E, Olivas V, et al. NF-κB-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer. Cell Rep. 2015;11:98-110.

214. Zahir N, Sun R, Gallahan D, Gatenby RA, Curtis C. Characterizing the ecological and evolutionary dynamics of cancer. Nat Genet. 2020;52:759-67.

215. Wang L, Lankhorst L, Bernards R. Exploiting senescence for the treatment of cancer. Nat Rev Cancer. 2022;22:340-55.

216. Schmitt CA, Wang B, Demaria M. Senescence and cancer - role and therapeutic opportunities. Nat Rev Clin Oncol. 2022;19:619-36.

217. Gatenby RA, Silva AS, Gillies RJ, Frieden BR. Adaptive therapy. Cancer Res. 2009;69:4894-903.

218. Gatenby RA, Brown JS. Integrating evolutionary dynamics into cancer therapy. Nat Rev Clin Oncol. 2020;17:675-86.

219. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582-98.

220. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23:277-86.

221. Isaacs JT, Antony L, Dalrymple SL, et al. Tasquinimod is an allosteric modulator of HDAC4 survival signaling within the compromised cancer microenvironment. Cancer Res. 2013;73:1386-99.

222. Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355:1152-8.

223. O’Sullivan CC, Moon DH, Kohn EC, Lee JM. Beyond breast and ovarian cancers: PARP inhibitors for BRCA mutation-associated and BRCA-like solid tumors. Front Oncol. 2014;4:42.

224. Rimkus TK, Carpenter RL, Qasem S, Chan M, Lo HW. Targeting the sonic hedgehog signaling pathway: review of smoothened and GLI inhibitors. Cancers. 2016;8:22.

225. Ngoi NYL, Gallo D, Torrado C, Nardo M, Durocher D, Yap TA. Synthetic lethal strategies for the development of cancer therapeutics. Nat Rev Clin Oncol. 2025;22:46-64.

226. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346-54.

227. McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168:613-28.

228. Sullivan R, Alatise OI, Anderson BO, et al. Global cancer surgery: delivering safe, affordable, and timely cancer surgery. Lancet Oncol. 2015;16:1193-224.

229. Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501:355-64.

230. Garraway LA, Jänne PA. Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov. 2012;2:214-26.

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