REFERENCES
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-63.
2. Sonkin D, Thomas A, Teicher BA. Cancer treatments: past, present, and future. Cancer Genet. 2024;286-7:18-24.
3. Hu Z, Ding J, Ma Z, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51:1113-22.
4. Van Cutsem E, Nordlinger B, Cervantes A; ESMO Guidelines Working Group. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010;21 Suppl 5:v93-7.
5. Chen P, Liu XQ, Lin X, Gao LY, Zhang S, Huang X. Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism. Mol Ther Oncolytics. 2021;20:228-39.
6. Yao CW, Kang KA, Piao MJ, et al. Reduced autophagy in 5-fluorouracil resistant colon cancer cells. Biomol Ther. 2017;25:315-20.
7. Gmeiner WH, Okechukwu CC. Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects. Cancer Drug Resist. 2023;6:257-72.
8. 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.
9. Li S, Li X, Yang X, et al. Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78. Sci Rep. 2023;13:22661.
10. Gao L, Shen L, Yu M, et al. Colon cancer cells treated with 5-fluorouracil exhibit changes in polylactosamine-type N-glycans. Mol Med Rep. 2014;9:1697-702.
11. Azwar S, Seow HF, Abdullah M, Faisal Jabar M, Mohtarrudin N. Recent updates on mechanisms of resistance to 5-fluorouracil and reversal strategies in colon cancer treatment. Biology. 2021;10:854.
12. Nakagawa Y, Kajihara A, Takahashi A, et al. The BRCA2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells. Oncol Rep. 2014;31:2001-6.
13. Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M. Targeting DNA damage response pathways in cancer. Nat Rev Cancer. 2023;23:78-94.
14. Bierbaum M, Bastiaens PI. Cell cycle-dependent binding modes of the ran exchange factor RCC1 to chromatin. Biophys J. 2013;104:1642-51.
15. Jing L, Kwok HF. The intricate roles of RCC1 in normal cells and cancer cells. Biochem Soc Trans. 2022;50:83-93.
16. Cekan P, Hasegawa K, Pan Y, et al. RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damage-induced cell senescence. Mol Biol Cell. 2016;27:1346-57.
17. Bannoura SF, Aboukameel A, Khan HY, et al. RCC1 regulation of subcellular protein localization via Ran GTPase drives pancreatic ductal adenocarcinoma growth. Cancer Lett. 2024;604:217275.
18. Liu H, Wang P. CRISPR screening and cell line IC50 data reveal novel key genes for trametinib resistance. Clin Exp Med. 2024;25:21.
19. Zhang K, Erkan EP, Jamalzadeh S, et al. Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer. Sci Adv. 2022;8:eabm1831.
20. Deng Y, Yu L, Zhao Y, et al. RCC1 expression as a prognostic marker in colorectal liver oligometastases. Pathol Oncol Res. 2021;27:1610077.
21. Qiao L, Zheng J, Tian Y, et al. Regulator of chromatin condensation 1 abrogates the G1 cell cycle checkpoint via Cdk1 in human papillomavirus E7-expressing epithelium and cervical cancer cells. Cell Death Dis. 2018;9:583.
22. Hou X, Qiao L, Liu R, Han X, Zhang W. Phosphorylation of RCC1 on serine 11 facilitates G1/S transition in HPV E7-expressing cells. Biomolecules. 2021;11:995.
23. Zhuang M, Li F, Liang H, et al. Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2. Cell Death Dis. 2024;15:241.
24. Renault L, Kuhlmann J, Henkel A, Wittinghofer A. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell. 2001;105:245-55.
25. Huang T, Yang Y, Song X, et al. PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells. Mol Cell. 2021;81:1276-91.e9.
26. Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024;42:946-67.
27. Aubrey BJ, Kelly GL, Janic A, Herold MJ, Strasser A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25:104-13.
28. Feng L, Hollstein M, Xu Y. Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence. Cell Cycle. 2006;5:2812-9.
29. Okamura S, Arakawa H, Tanaka T, et al. p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Mol Cell. 2001;8:85-94.
30. Oda K, Arakawa H, Tanaka T, et al. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell. 2000;102:849-62.
31. Maiuthed A, Ninsontia C, Erlenbach-Wuensch K, et al. Cytoplasmic p21 mediates 5-fluorouracil resistance by inhibiting pro-apoptotic Chk2. Cancers. 2018;10:373.
32. Yang H, Huebner K, Hampel C, et al. ATF2 loss promotes 5-FU resistance in colon cancer cells via activation of the ATR-Chk1 damage response pathway. BMC Cancer. 2023;23:480.
33. Huang RX, Zhou PK. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct Target Ther. 2020;5:60.
34. Shimada E, Matsumoto Y, Nakagawa M, et al. Methylation-mediated silencing of protein kinase C zeta induces apoptosis avoidance through ATM/CHK2 inactivation in dedifferentiated chondrosarcoma. Br J Cancer. 2022;126:1289-300.
35. Joe Y, Jeong JH, Yang S, et al. ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis. J Biol Chem. 2006;281:28764-71.
36. Rogoff HA, Pickering MT, Frame FM, et al. Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm/Nbs1/Chk2. Mol Cell Biol. 2004;24:2968-77.
37. Stevens C, Smith L, La Thangue NB. Chk2 activates E2F-1 in response to DNA damage. Nat Cell Biol. 2003;5:401-9.
38. Yang S, Kuo C, Bisi JE, Kim MK. PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol. 2002;4:865-70.
39. Chen WS, Lee YJ, Yu YC, et al. Enhancement of p53-mutant human colorectal cancer cells radiosensitivity by flavonoid fisetin. Int J Radiat Oncol Biol Phys. 2010;77:1527-35.
40. Hsieh CC, Hsu SH, Lin CY, et al. CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer. Br J Cancer. 2022;127:1615-28.
41. Martin SA, Ouchi T. Cellular commitment to reentry into the cell cycle after stalled DNA is determined by site-specific phosphorylation of Chk1 and PTEN. Mol Cancer Ther. 2008;7:2509-16.
42. Liu Y, Tseng M, Perdreau SA, et al. Histone H2AX is a mediator of gastrointestinal stromal tumor cell apoptosis following treatment with imatinib mesylate. Cancer Res. 2007;67:2685-92.
43. Siddiqui MS, François M, Fenech MF, Leifert WR. Persistent γH2AX: a promising molecular marker of DNA damage and aging. Mutat Res Rev Mutat Res. 2015;766:1-19.
44. Carvalho JF, Kanaar R. Targeting homologous recombination-mediated DNA repair in cancer. Expert Opin Ther Targets. 2014;18:427-58.
45. Karanam K, Kafri R, Loewer A, Lahav G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol Cell. 2012;47:320-9.
46. Cybulla E, Vindigni A. Leveraging the replication stress response to optimize cancer therapy. Nat Rev Cancer. 2023;23:6-24.
47. Drew Y, Zenke FT, Curtin NJ. DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications. Nat Rev Drug Discov. 2025;24:19-39.
48. Fradet-Turcotte A, Sitz J, Grapton D, Orthwein A. BRCA2 functions: from DNA repair to replication fork stabilization. Endocr Relat Cancer. 2016;23:T1-17.
49. Schlacher K, Wu H, Jasin M. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell. 2012;22:106-16.
50. Lomonosov M, Anand S, Sangrithi M, Davies R, Venkitaraman AR. Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein. Genes Dev. 2003;17:3017-22.
51. Neal FE, Li W, Uhrig ME, et al. Distinct roles of the two BRCA2 DNA-binding domains in DNA damage repair and replication fork preservation. Cell Rep. 2025;44:115654.
52. Salunkhe S, Daley JM, Kaur H, et al. Promotion of DNA end resection by BRCA1-BARD1 in homologous recombination. Nature. 2024;634:482-91.
53. Ceppi I, Dello Stritto MR, Mütze M, et al. Mechanism of BRCA1-BARD1 function in DNA end resection and DNA protection. Nature. 2024;634:492-500.
54. Tarsounas M, Sung P. The antitumorigenic roles of BRCA1-BARD1 in DNA repair and replication. Nat Rev Mol Cell Biol. 2020;21:284-99.
55. Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008;18:99-113.
56. Matos-Rodrigues G, Barroca V, Muhammad AA, et al.
57. Xu X, Xu Y, Guo R, et al. Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress. Nat Struct Mol Biol. 2021;28:487-500.
58. Engel JL, Zhang X, Wu M, et al. The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance. Cell. 2024;187:6055-70.e22.
59. Erdemir Sayan S, Sreekumar R, Bhome R, Mirnezami A, Yagci T, Sayan AE. ERCC1 abundance is an indicator of DNA repair-apoptosis decision upon DNA damage. Cell Death Discov. 2024;10:47.
60. Lehmann J, Seebode C, Smolorz S, Schubert S, Emmert S. XPF knockout via CRISPR/Cas9 reveals that ERCC1 is retained in the cytoplasm without its heterodimer partner XPF. Cell Mol Life Sci. 2017;74:2081-94.








