CoChat
Sign Up
Cited by 184

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer

Gu, Yixiang, Yang, Ruifeng, Zhang, Yang, Guo, Miaomiao, Takehiro, Kyle, Zhan, Ming, Yang, Linhua, Wang, Hui·2025·Molecular Biomedicine
DOI 10.1186/s43556-024-00239-2PMC PMC11700966
Open this paper in CoChat — free account

Abstract

Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s43556-024-00239-2

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 General mechanisms of cancer chemoresistance. Upon exposure to chemotherapeutic agents, tumors initiate multiple mechanisms that mediate chemoresistance. Here, we delineate the molecular pathways involved in cancer chemoresistance, including: drug efflux, DNA damage repair, apoptosis evasion, epigenetic modifications, Altered Drug Metabolism, Cancer Stem Cells (CSCs)
Fig. 1 General mechanisms of cancer chemoresistance. Upon exposure to chemotherapeutic agents, tumors initiate multiple mechanisms that mediate chemoresistance. Here, we delineate the molecular pathways involved in cancer chemoresistance, including: drug efflux, DNA damage repair, apoptosis evasion, epigenetic modifications, Altered Drug Metabolism, Cancer Stem Cells (CSCs)CC BY · PubMed Central
Fig. 2 Apoptosis Evasion as a Mechanism of Chemoresistance. Chemotherapeutic intervention in tumor cells activates the intrinsic protective autophagy system. Concurrently, dysregulated expression and mutations in Bcl-2, IAP, and NF-κB family proteins impair chemotherapy-induced apoptosis in tumor cells. These factors collectively enable apoptosis evasion, leading to enhanced chemoresistance
Fig. 2 Apoptosis Evasion as a Mechanism of Chemoresistance. Chemotherapeutic intervention in tumor cells activates the intrinsic protective autophagy system. Concurrently, dysregulated expression and mutations in Bcl-2, IAP, and NF-κB family proteins impair chemotherapy-induced apoptosis in tumor cells. These factors collectively enable apoptosis evasion, leading to enhanced chemoresistanceCC BY · PubMed Central
Fig. 3 Overview of epigenetic modifications involved in cancer. (1) DNA methylation. Through the catalytic activity of DNMTs, cytosine residues are selectively methylated, producing 5-methylcytosine (5-mC). Methylation in promoter regions effectively downregulates the transcription of target genes, ultimately restricting the translation of mRNA into proteins. (2) Histone modifications. (a) (de)methylation. Histone methylation and demethylation, mediated by HMTs and HDMs, indirectly modulate chromatin accessibility and gene expression by altering the binding affinities of other epigenetic regulators. (b)(de)acetylation. Histone acetylation and deacetylation, catalyzed by HATs and HDACs, induce structural alterations in chromatin, thereby modulating gene expression. (c)(de)phosphorylation. Through the catalytic activities of PKs and PPs, histones undergo phosphorylation and dephosphorylation, facilitating rapid adjustments in chromatin structure and gene expression in response to cellular conditions and demands. (3) ncRNAs regulation. miRNA binds to the 3’ untranslated region (3’-UTR) of target mRNAs, typically leading to mRNA degradation or translational repression, which in turn reduces target protein expression. Conversely, lncRNA can act as a “miRNA sponge” by binding to miRNAs, preventing them from associating with their target mRNAs and thus promoting the expression of specific mRNAs
Fig. 3 Overview of epigenetic modifications involved in cancer. (1) DNA methylation. Through the catalytic activity of DNMTs, cytosine residues are selectively methylated, producing 5-methylcytosine (5-mC). Methylation in promoter regions effectively downregulates the transcription of target genes, ultimately restricting the translation of mRNA into proteins. (2) Histone modifications. (a) (de)methylation. Histone methylation and demethylation, mediated by HMTs and HDMs, indirectly modulate chromatin accessibility and gene expression by altering the binding affinities of other epigenetic regulators. (b)(de)acetylation. Histone acetylation and deacetylation, catalyzed by HATs and HDACs, induce structural alterations in chromatin, thereby modulating gene expression. (c)(de)phosphorylation. Through the catalytic activities of PKs and PPs, histones undergo phosphorylation and dephosphorylation, facilitating rapid adjustments in chromatin structure and gene expression in response to cellular conditions and demands. (3) ncRNAs regulation. miRNA binds to the 3’ untranslated region (3’-UTR) of target mRNAs, typically leading to mRNA degradation or translational repression, which in turn reduces target protein expression. Conversely, lncRNA can act as a “miRNA sponge” by binding to miRNAs, preventing them from associating with their target mRNAs and thus promoting the expression of specific mRNAsCC BY · PubMed Central
Fig. 4 Cancer stem cell model. Tumor tissues contain CSCs, a subpopulation with self-renewing properties. When chemotherapy is applied, typical cancer cells undergo apoptosis, yet CSCs evade these effects, leading to their survival and the possibility of treatment resistance
Fig. 4 Cancer stem cell model. Tumor tissues contain CSCs, a subpopulation with self-renewing properties. When chemotherapy is applied, typical cancer cells undergo apoptosis, yet CSCs evade these effects, leading to their survival and the possibility of treatment resistanceCC BY · PubMed Central
Fig. 5 Novel strategies to overcome chemoresistance in cancer. a Combination therapy. Combining chemotherapy with other modalities improves therapeutic outcomes. b Targeting the tumor microenvironment (TME). The TME serves as a formidable barrier that chemotherapeutic agents must overcome to achieve therapeutic efficacy. c Drug delivery systems. Various carriers can enhance drug delivery, addressing issues of poor targeting and increased toxicity. d Personalized medicine. Analyzing genetic composition allows for the customization of therapies to achieve the greatest treatment benefit
Fig. 5 Novel strategies to overcome chemoresistance in cancer. a Combination therapy. Combining chemotherapy with other modalities improves therapeutic outcomes. b Targeting the tumor microenvironment (TME). The TME serves as a formidable barrier that chemotherapeutic agents must overcome to achieve therapeutic efficacy. c Drug delivery systems. Various carriers can enhance drug delivery, addressing issues of poor targeting and increased toxicity. d Personalized medicine. Analyzing genetic composition allows for the customization of therapies to achieve the greatest treatment benefitCC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 20 references

Research works printed but not linked: 237

  1. 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(16):3029–30. https://doi.org/10.1002/cncr.33587. · DOI
  2. Krell RW, Wei AC. Gallbladder cancer: surgical management. Chin Clin Oncol. 2019;8(4):36. https://doi.org/10.21037/cco.2019.06.06. · DOI
  3. Hickman L, Contreras C. Gallbladder Cancer: Diagnosis, Surgical Management, and Adjuvant Therapies. Surg Clin North Am. 2019;99(2):337–55. https://doi.org/10.1016/j.suc.2018.12.008. · DOI
  4. Vogel A, Bridgewater J, Edeline J, Kelley RK, Klümpen HJ, Malka D, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(2):127–40. https://doi.org/10.1016/j.annonc.2022.10.506. · DOI
  5. Luo D, Yang Y, Zhang R, Li Q, Li X. Effect of interval between neoadjuvant chemoradiotherapy and surgery on oncological outcomes in poor responders with locally advanced rectal cancer: a retrospective cohort study. Int J Surg. 2023;109(7):1993–2000. https://doi.org/10.1097/js9.0000000000000438. · DOI
  6. Zhuang Z, Yilihamu A, Li Z, Lei R, Li X, Han M et al. The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study. J Natl Compr Canc Netw. 2024:1–7. https://doi.org/10.6004/jnccn.2024.7023. · DOI
  7. Noronha V, Patil VM, Menon N, Goud S, Singh A, Shah M, et al. Phase III randomized trial comparing palliative systemic therapy to best supportive care in advanced esophageal/GEJ cancer. Int J Cancer. 2024. https://doi.org/10.1002/ijc.35111. · DOI
  8. Yuan X, Guan D, Chen C, Guo S, Wu H, Bu H, et al. Development of an Imidazopyridazine-Based MNK1/2 Inhibitor for the Treatment of Lymphoma. J Med Chem. 2024;67(7):5437–57. https://doi.org/10.1021/acs.jmedchem.3c02008. · DOI
  9. Ramos A, Sadeghi S, Tabatabaeian H. Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. Int J Mol Sci. 2021;22(17). https://doi.org/10.3390/ijms22179451. · DOI
  10. Lippert TH, Ruoff HJ, Volm M. Intrinsic and acquired drug resistance in malignant tumors. The main reason for therapeutic failure. Arzneimittelforschung. 2008;58(6):261–4. https://doi.org/10.1055/s-0031-1296504. · DOI
  11. Zheng HC. The molecular mechanisms of chemoresistance in cancers. Oncotarget. 2017;8(35):59950–64. https://doi.org/10.18632/oncotarget.19048. · DOI
  12. Pan ST, Li ZL, He ZX, Qiu JX, Zhou SF. Molecular mechanisms for tumour resistance to chemotherapy. Clin Exp Pharmacol Physiol. 2016;43(8):723–37. https://doi.org/10.1111/1440-1681.12581. · DOI
  13. Liu X. ABC Family Transporters. Adv Exp Med Biol. 2019;1141:13–100. https://doi.org/10.1007/978-981-13-7647-4_2. · DOI
  14. Lusvarghi S, Robey RW, Gottesman MM, Ambudkar SV. Multidrug transporters: recent insights from cryo-electron microscopy-derived atomic structures and animal models. F1000Res. 2020;9. https://doi.org/10.12688/f1000research.21295.1. · DOI
  15. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018;18(7):452–64. https://doi.org/10.1038/s41568-018-0005-8. · DOI · Paper page
  16. Morau MV, Seguin CS, Visacri MB, Pincinato EC, Moriel P. Genetic Variants in the ABCB1 and ABCG2 Gene Drug Transporters Involved in Gefitinib-Associated Adverse Reaction: A Systematic Review and Meta-Analysis. Genes (Basel). 2024;15(5). https://doi.org/10.3390/genes15050591. · DOI
  17. Li Q, Mou LJ, Tao L, Chen W, Sun XT, Xia XF, et al. Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression. Eur Rev Med Pharmacol Sci. 2016;20(9):1699–706.
  18. Wang H, Zhan M, Xu SW, Chen W, Long MM, Shi YH, et al. miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer. Cell Death Dis. 2017;8(5): e2770. https://doi.org/10.1038/cddis.2017.178. · DOI
  19. Eisa A, Hanafy SM, Khalil H, Elshal MF. Sitagliptin synergizes 5-fluorouracil efficacy in colon cancer cells through MDR1-mediated flux impairment and down regulation of NFκB2 and p-AKT survival proteins. J Biochem Mol Toxicol. 2024;38(8): e23796. https://doi.org/10.1002/jbt.23796. · DOI
  20. Yang Z, Chen F, Wei D, Chen F, Jiang H, Qin S. EGR1 mediates MDR1 transcriptional activity regulating gemcitabine resistance in pancreatic cancer. BMC Cancer. 2024;24(1):268. https://doi.org/10.1186/s12885-024-12005-2. · DOI
  21. Zhan M, Wang H, Chen T, Chen W, Yang L, He M, et al. NOX1 mediates chemoresistance via HIF1α/MDR1 pathway in gallbladder cancer. Biochem Biophys Res Commun. 2015;468(1–2):79–85. https://doi.org/10.1016/j.bbrc.2015.10.161. · DOI
  22. Dong Q, Zhou C, Ren H, Zhang Z, Cheng F, Xiong Z, et al. Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells. Cell Commun Signal. 2020;18(1):167. https://doi.org/10.1186/s12964-020-00653-3. · DOI
  23. Zhang X, Gu G, Song L, Wang D, Xu Y, Yang S, et al. ID4 Promotes Breast Cancer Chemotherapy Resistance via CBF1-MRP1 Pathway. J Cancer. 2020;11(13):3846–57. https://doi.org/10.7150/jca.31988. · DOI
  24. Zhan M, Zhao X, Wang H, Chen W, Xu S, Wang W, et al. miR-145 sensitizes gallbladder cancer to cisplatin by regulating multidrug resistance associated protein 1. Tumour Biol. 2016;37(8):10553–62. https://doi.org/10.1007/s13277-016-4957-6. · DOI
  25. Wang H, Li X, Chen T, Wang W, Liu Q, Li H, et al. Mechanisms of verapamil-enhanced chemosensitivity of gallbladder cancer cells to platinum drugs: glutathione reduction and MRP1 downregulation. Oncol Rep. 2013;29(2):676–84. https://doi.org/10.3892/or.2012.2156. · DOI
  26. Pote MS, Gacche RN. ATP-binding cassette efflux transporters and MDR in cancer. Drug Discov Today. 2023;28(5): 103537. https://doi.org/10.1016/j.drudis.2023.103537. · DOI
  27. Feng M, Fan X, Shi J, Shan S, Li S, He S, et al. Terpenoids from quinoa reverse drug resistance of colon cancer by upregulating miR-495-3p. J Sci Food Agric. 2024. https://doi.org/10.1002/jsfa.13718. · DOI
  28. Zhao CC, Sun X, Chen J, Geng BD. NAT10-mediated mRNA N4-acetylcytidine modification of MDR1 and BCRP promotes breast cancer progression. Thorac Cancer. 2024;15(10):820–9. https://doi.org/10.1111/1759-7714.15262. · DOI
  29. Uceda-Castro R, Margarido AS, Song JY, de Gooijer MC, Messal HA, Chambers CR, et al. BCRP drives intrinsic chemoresistance in chemotherapy-naïve breast cancer brain metastasis. Sci Adv. 2023;9(42):eabp9530. https://doi.org/10.1126/sciadv.abp9530. · DOI
  30. Kalayda GV, Wagner CH, Buss I, Reedijk J, Jaehde U. Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells. BMC Cancer. 2008;8:175. https://doi.org/10.1186/1471-2407-8-175. · DOI
  31. Xiao F, Li Y, Wan Y, Xue M. MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy through regulation of ATP7A/B. Cancer Chemother Pharmacol. 2018;81(5):935–47. https://doi.org/10.1007/s00280-018-3548-1. · DOI
  32. Federica G, Michela C, Giovanna D. Targeting the DNA damage response in cancer. MedComm. 2024;5(11):e788. https://doi.org/10.1002/mco2.788. · DOI
  33. Jeppesen DK, Bohr VA, Stevnsner T. DNA repair deficiency in neurodegeneration. Prog Neurobiol. 2011;94(2):166–200. https://doi.org/10.1016/j.pneurobio.2011.04.013. · DOI
  34. Vickridge E, Faraco CCF, Nepveu A. Base excision repair accessory factors in senescence avoidance and resistance to treatments. Cancer Drug Resist. 2022;5(3):703–20. https://doi.org/10.20517/cdr.2022.36. · DOI
  35. Chen X, Li WF, Wu X, Zhang HC, Chen L, Zhang PY, et al. Dicer regulates non-homologous end joining and is associated with chemosensitivity in colon cancer patients. Carcinogenesis. 2017;38(9):873–82. https://doi.org/10.1093/carcin/bgx059. · DOI
  36. Wei S, Han C, Mo S, Huang H, Luo X. Advancements in programmed cell death research in antitumor therapy: a comprehensive overview. Apoptosis. 2024. https://doi.org/10.1007/s10495-024-02038-0. · DOI
  37. Fang J, Ye Z, Gu F, Yan M, Lin Q, Lin J, et al. DUSP1 enhances the chemoresistance of gallbladder cancer via the modulation of the p38 pathway and DNA damage/repair system. Oncol Lett. 2018;16(2):1869–75. https://doi.org/10.3892/ol.2018.8822. · DOI
  38. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013. · DOI · Paper page
  39. Yamamoto K, Iwadate D, Naito E, Tateishi K, Fujishiro M. Autophagy as a critical driver of metabolic adaptation, therapeutic resistance, and immune evasion of cancer. Curr Opin Biotechnol. 2023;84: 103012. https://doi.org/10.1016/j.copbio.2023.103012. · DOI
  40. Pimentel JM, Zhou JY, Wu GS. Autophagy and cancer therapy. Cancer Lett. 2024;605: 217285. https://doi.org/10.1016/j.canlet.2024.217285. · DOI
  41. Xu Y, Yu H, Qin H, Kang J, Yu C, Zhong J, et al. Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells. Cancer Lett. 2012;314(2):232–43. https://doi.org/10.1016/j.canlet.2011.09.034. · DOI
  42. Yang B, Li Y, Zhang R, Liu L, Miao H, Li Y, et al. MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma. Am J Cancer Res. 2020;10(11):3896–910.
  43. Wang S, Feng W, Wang W, Ye X, Chen H, Yu C. Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy. Front Oncol. 2021;11: 618764. https://doi.org/10.3389/fonc.2021.618764. · DOI
  44. Wang FT, Wang H, Wang QW, Pan MS, Li XP, Sun W, et al. Inhibition of autophagy by chloroquine enhances the antitumor activity of gemcitabine for gallbladder cancer. Cancer Chemother Pharmacol. 2020;86(2):221–32. https://doi.org/10.1007/s00280-020-04100-5. · DOI
  45. Chen N, Qi Y, Ma X, Xiao X, Liu Q, Xia T, et al. Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine. Front Pharmacol. 2022;13: 906301. https://doi.org/10.3389/fphar.2022.906301. · DOI
  46. Kaur S, Mendonca P, Soliman KFA. The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer. Nutrients. 2024;16(15). https://doi.org/10.3390/nu16152392. · DOI
  47. Urrutia S, Takahashi K. Precision medicine in AML: overcoming resistance. Int J Hematol. 2024. https://doi.org/10.1007/s12185-024-03827-8. · DOI
  48. Yuan J, Lan H, Jiang X, Zeng D, Xiao S. Bcl-2 family: Novel insight into individualized therapy for ovarian cancer (Review). Int J Mol Med. 2020;46(4):1255–65. https://doi.org/10.3892/ijmm.2020.4689. · DOI
  49. Zhang J, Wang Y, Yin C, Gong P, Zhang Z, Zhao L, et al. Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis. Cell Death Dis. 2022;13(4):379. https://doi.org/10.1038/s41419-022-04810-z. · DOI
  50. Miquel C, Borrini F, Grandjouan S, Aupérin A, Viguier J, Velasco V, et al. Role of bax mutations in apoptosis in colorectal cancers with microsatellite instability. Am J Clin Pathol. 2005;123(4):562–70. https://doi.org/10.1309/jq2x-3rv3-l8f9-tgyw. · DOI
  51. Carter JL, Su Y, Qiao X, Zhao J, Wang G, Howard M, et al. Acquired resistance to venetoclax plus azacitidine in acute myeloid leukemia: In vitro models and mechanisms. Biochem Pharmacol. 2023;216: 115759. https://doi.org/10.1016/j.bcp.2023.115759. · DOI
  52. Carter BZ, Mak PY, Tao W, Zhang Q, Ruvolo V, Kuruvilla VM, et al. Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic-Resistant AML and AML Stem Cells. Mol Cancer Ther. 2022;21(6):879–89. https://doi.org/10.1158/1535-7163.Mct-21-0690. · DOI
  53. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, et al. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2005;102(1):105–10. https://doi.org/10.1073/pnas.0408352102. · DOI
  54. Cetraro P, Plaza-Diaz J, MacKenzie A, Abadía-Molina F. A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer. Cancers (Basel). 2022;14(7). https://doi.org/10.3390/cancers14071671. · DOI
  55. Rathore R, McCallum JE, Varghese E, Florea AM, Büsselberg D. Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs). Apoptosis. 2017;22(7):898–919. https://doi.org/10.1007/s10495-017-1375-1. · DOI
  56. Guo Q, Jin Y, Lin M, Zeng C, Zhang J. NF-κB signaling in therapy resistance of breast cancer: Mechanisms, approaches, and challenges. Life Sci. 2024;348: 122684. https://doi.org/10.1016/j.lfs.2024.122684. · DOI
  57. Yang MH, Lee KT, Yang S, Lee JK, Lee KH, Moon IH, et al. Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-κB. J Cancer Res Clin Oncol. 2012;138(10):1743–51. https://doi.org/10.1007/s00432-012-1254-7. · DOI
  58. Nwabo Kamdje AH, Dongmo Fogang HP, Mimche PN. Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy. Front Mol Med. 2024;4:1426454. https://doi.org/10.3389/fmmed.2024.1426454. · DOI
  59. Panda R, Mohan S, Vellapandian C. Harnessing Epigenetic Mechanisms to Overcome Immune Evasion in Cancer: The Current Strategies and Future Directions. Cureus. 2024;16(10): e70631. https://doi.org/10.7759/cureus.70631. · DOI
  60. Urban T, Pokorná P, Slabý O. Significance of aberrant DNA methylation for cancer diagnostics and therapy. Klin Onkol. 2024;38(2):88–94. https://doi.org/10.48095/ccko202488. · DOI
  61. Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA. 2011;306(14):1557–65. https://doi.org/10.1001/jama.2011.1456. · DOI · Paper page
  62. Kang SH, Bang YJ, Im YH, Yang HK, Lee DA, Lee HY, et al. Transcriptional repression of the transforming growth factor-beta type I receptor gene by DNA methylation results in the development of TGF-beta resistance in human gastric cancer. Oncogene. 1999;18(51):7280–6. https://doi.org/10.1038/sj.onc.1203146. · DOI
  63. Zhang X, Yashiro M, Ohira M, Ren J, Hirakawa K. Synergic antiproliferative effect of DNA methyltransferase inhibitor in combination with anticancer drugs in gastric carcinoma. Cancer Sci. 2006;97(9):938–44. https://doi.org/10.1111/j.1349-7006.2006.00253.x. · DOI
  64. Stefansson OA, Esteller M. Epigenetic modifications in breast cancer and their role in personalized medicine. Am J Pathol. 2013;183(4):1052–63. https://doi.org/10.1016/j.ajpath.2013.04.033. · DOI
  65. Skouras P, Markouli M, Papadatou I, Piperi C. Targeting epigenetic mechanisms of resistance to chemotherapy in gliomas. Crit Rev Oncol Hematol. 2024;204: 104532. https://doi.org/10.1016/j.critrevonc.2024.104532. · DOI
  66. Reyes ME, Pulgar V, Vivallo C, Ili CG, Mora-Lagos B, Brebi P. Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance. Front Immunol. 2024;15:1347530. https://doi.org/10.3389/fimmu.2024.1347530. · DOI
  67. Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol. 2014;6(4): a018713. https://doi.org/10.1101/cshperspect.a018713. · DOI
  68. Ono H, Basson MD, Ito H. P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. Oncotarget. 2016;7(32):51301–10. https://doi.org/10.18632/oncotarget.10117. · DOI
  69. Kim MG, Pak JH, Choi WH, Park JY, Nam JH, Kim JH. The relationship between cisplatin resistance and histone deacetylase isoform overexpression in epithelial ovarian cancer cell lines. J Gynecol Oncol. 2012;23(3):182–9. https://doi.org/10.3802/jgo.2012.23.3.182. · DOI
  70. Vagapova E, Kozlov M, Lebedev T, Ivanenko K, Leonova O, Popenko V et al. Selective Inhibition of HDAC Class I Sensitizes Leukemia and Neuroblastoma Cells to Anticancer Drugs. Biomedicines. 2021;9(12). https://doi.org/10.3390/biomedicines9121846. · DOI
  71. Hu S, Yu L, Li Z, Shen Y, Wang J, Cai J, et al. Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo. Cancer Biol Ther. 2010;10(8):788–95. https://doi.org/10.4161/cbt.10.8.12913. · DOI
  72. Zhang L, Zhang X, Shi Y, Ni Y, Fei J, Jin Z, et al. Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer. Front Oncol. 2024;14:1376916. https://doi.org/10.3389/fonc.2024.1376916. · DOI
  73. Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 2021;65(4):625–39. https://doi.org/10.1042/ebc20200032. · DOI
  74. Rahdan F, Saberi A, Saraygord-Afshari N, Hadizadeh M, Fayeghi T, Ghanbari E, et al. Deciphering the multifaceted role of microRNAs in hepatocellular carcinoma: Integrating literature review and bioinformatics analysis for therapeutic insights. Heliyon. 2024;10(20): e39489. https://doi.org/10.1016/j.heliyon.2024.e39489. · DOI
  75. Long M, Zhan M, Xu S, Yang R, Chen W, Zhang S, et al. miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer. Mol Cancer. 2017;16(1):167. https://doi.org/10.1186/s12943-017-0723-7. · DOI
  76. Shahin RK, Elkady MA, Abulsoud AI, Abdelmaksoud NM, Abdel Mageed SS, El-Dakroury WA, et al. miRNAs orchestration of gallbladder cancer - Particular emphasis on diagnosis, progression and drug resistance. Pathol Res Pract. 2023;248: 154684. https://doi.org/10.1016/j.prp.2023.154684. · DOI
  77. Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2016;17(1):47–62. https://doi.org/10.1038/nrg.2015.10. · DOI
  78. Chen LL. Linking Long Noncoding RNA Localization and Function. Trends Biochem Sci. 2016;41(9):761–72. https://doi.org/10.1016/j.tibs.2016.07.003. · DOI
  79. Cai Q, Wang S, Jin L, Weng M, Zhou D, Wang J, et al. Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy. Mol Cancer. 2019;18(1):82. https://doi.org/10.1186/s12943-019-1016-0. · DOI
  80. Gao K, Chen S, Yang X. HOTTIP Enhances Gemcitabine and Cisplatin Resistance Through Sponging miR-637 in Cholangiocarcinoma. Front Oncol. 2021;11: 664916. https://doi.org/10.3389/fonc.2021.664916. · DOI
  81. Yang D, Zhan M, Chen T, Chen W, Zhang Y, Xu S, et al. miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer. Sci Rep. 2017;7:43109. https://doi.org/10.1038/srep43109. · DOI
  82. Li M, Chen W, Zhang H, Zhang Y, Ke F, Wu X, et al. MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer. Oncotarget. 2016;7(50):83060–70. https://doi.org/10.18632/oncotarget.13067. · DOI
  83. Zhang GF, Wu JC, Wang HY, Jiang WD, Qiu L. Overexpression of microRNA-205-5p exerts suppressive effects on stem cell drug resistance in gallbladder cancer by down-regulating PRKCE. Biosci Rep. 2020;40(9). https://doi.org/10.1042/bsr20194509. · DOI
  84. Yang G, Xu Q, Wan Y, Zhang L, Wang Z, Meng F. miR-193a-3p Enhanced the Chemosensitivity to Trametinib in Gallbladder Carcinoma by Targeting KRAS and Downregulating ERK Signaling. Cancer Biother Radiopharm. 2023;38(6):371–9. https://doi.org/10.1089/cbr.2021.0016. · DOI
  85. Yu J, Zhang W, Lu B, Qian H, Tang H, Zhu Z, et al. miR-433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M. Oncol Lett. 2018;15(3):3305–12. https://doi.org/10.3892/ol.2017.7708. · DOI
  86. Lu W, Hu Y, Ma Q, Zhou L, Jiang L, Li Z, et al. miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1. Oncotarget. 2016;7(38):62364–76. https://doi.org/10.18632/oncotarget.11634. · DOI
  87. Li Y, Tian M, Zhang D, Zhuang Y, Li Z, Xie S, et al. Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation. Cancer Manag Res. 2021;13:6219–30. https://doi.org/10.2147/cmar.S323759. · DOI
  88. Kaur G, Gupta SK, Singh P, Ali V, Kumar V, Verma M. Drug-metabolizing enzymes: role in drug resistance in cancer. Clin Transl Oncol. 2020;22(10):1667–80. https://doi.org/10.1007/s12094-020-02325-7. · DOI
  89. Tabur S, Oztuzcu S, Oguz E, Demiryürek S, Dagli H, Alasehirli B, et al. CYP gene expressions in obesity-associated metabolic syndrome. Obes Res Clin Pract. 2016;10(6):719–23. https://doi.org/10.1016/j.orcp.2016.03.001. · DOI
  90. Valencia-Cervantes J, Huerta-Yepez S, Aquino-Jarquín G, Rodríguez-Enríquez S, Martínez-Fong D, Arias-Montaño JA, et al. Hypoxia increases chemoresistance in human medulloblastoma DAOY cells via hypoxia-inducible factor 1α-mediated downregulation of the CYP2B6, CYP3A4 and CYP3A5 enzymes and inhibition of cell proliferation. Oncol Rep. 2019;41(1):178–90. https://doi.org/10.3892/or.2018.6790. · DOI
  91. Torres-Zárate C, Vences-Mejía A, Espinosa-Aguirre JJ, Díaz-Díaz E, Palacios-Acosta JM, Cárdenas-Cardós R, et al. Expression of Cytochrome P450 Enzymes in Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Possible Role in Carcinogenesis and Treatment Response. Int J Toxicol. 2022;41(3):234–42. https://doi.org/10.1177/10915818221085909. · DOI
  92. Marengo B, Pulliero A, Izzotti A, Domenicotti C. miRNA Regulation of Glutathione Homeostasis in Cancer Initiation. Progression and Therapy Resistance Microrna. 2020;9(3):187–97. https://doi.org/10.2174/2211536609666191218103220. · DOI
  93. Zhang T, Yao C, Zhou X, Liu S, Qi L, Zhu S et al. Glutathione‑degrading enzymes in the complex landscape of tumors (Review). Int J Oncol. 2024;65(1). https://doi.org/10.3892/ijo.2024.5660. · DOI
  94. Ueno H, Kiyosawa K, Kaniwa N. Pharmacogenomics of gemcitabine: can genetic studies lead to tailor-made therapy? Br J Cancer. 2007;97(2):145–51. https://doi.org/10.1038/sj.bjc.6603860. · DOI
  95. Nakano T, Saiki Y, Kudo C, Hirayama A, Mizuguchi Y, Fujiwara S, et al. Acquisition of chemoresistance to gemcitabine is induced by a loss-of-function missense mutation of DCK. Biochem Biophys Res Commun. 2015;464(4):1084–9. https://doi.org/10.1016/j.bbrc.2015.07.080. · DOI
  96. Lu SC. Regulation of hepatic glutathione synthesis: current concepts and controversies. Faseb j. 1999;13(10):1169–83. · DOI
  97. Aponte PM, Caicedo A. Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment. Stem Cells Int. 2017;2017:5619472. https://doi.org/10.1155/2017/5619472. · DOI
  98. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23(10):1124–34. https://doi.org/10.1038/nm.4409. · DOI · Paper page
  99. Gires O. Lessons from common markers of tumor-initiating cells in solid cancers. Cell Mol Life Sci. 2011;68(24):4009–22. https://doi.org/10.1007/s00018-011-0772-9. · DOI
  100. Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci. 2019;234: 116781. https://doi.org/10.1016/j.lfs.2019.116781. · DOI
  101. Shi C, Tian R, Wang M, Wang X, Jiang J, Zhang Z, et al. CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol Ther. 2010;10(11):1182–90. https://doi.org/10.4161/cbt.10.11.13664. · DOI
  102. Desai A, Webb B, Gerson SL. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells. Radiother Oncol. 2014;110(3):538–45. https://doi.org/10.1016/j.radonc.2013.10.040. · DOI
  103. Wu Z, Miao X, Zhang Y, Li D, Zou Q, Yuan Y, et al. XRCC1 Is a Promising Predictive Biomarker and Facilitates Chemo-Resistance in Gallbladder Cancer. Front Mol Biosci. 2020;7:70. https://doi.org/10.3389/fmolb.2020.00070. · DOI
  104. Wang Y, Qi H, Liu Y, Duan C, Liu X, Xia T, et al. The double-edged roles of ROS in cancer prevention and therapy. Theranostics. 2021;11(10):4839–57. https://doi.org/10.7150/thno.56747. · DOI
  105. Donadelli M, Dando I, Zaniboni T, Costanzo C, Dalla Pozza E, Scupoli MT, et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2011;2(4): e152. https://doi.org/10.1038/cddis.2011.36. · DOI
  106. Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology. 2008;135(4):1358–68, 68.e1-4. https://doi.org/10.1053/j.gastro.2008.06.082. · DOI
  107. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, ME LL. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12(1):376–90. https://doi.org/10.1016/j.arr.2012.10.004. · DOI
  108. Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014;14(9):611–22. https://doi.org/10.1038/nrc3793. · DOI
  109. De Angelis ML, Francescangeli F, La Torre F, Zeuner A. Stem Cell Plasticity and Dormancy in the Development of Cancer Therapy Resistance. Front Oncol. 2019;9:626. https://doi.org/10.3389/fonc.2019.00626. · DOI
  110. Vassalli G. Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells. Stem Cells Int. 2019;2019:3904645. https://doi.org/10.1155/2019/3904645. · DOI
  111. Pors K, Moreb JS. Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development? Drug Discov Today. 2014;19(12):1953–63. https://doi.org/10.1016/j.drudis.2014.09.009. · DOI
  112. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene. 2008;27(12):1749–58. https://doi.org/10.1038/sj.onc.1210811. · DOI
  113. Huang J, Deng Y, Tin MS, Lok V, Ngai CH, Zhang L, et al. Distribution, Risk Factors, and Temporal Trends for Lung Cancer Incidence and Mortality: A Global Analysis. Chest. 2022;161(4):1101–11. https://doi.org/10.1016/j.chest.2021.12.655. · DOI
  114. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398(10299):535–54. https://doi.org/10.1016/s0140-6736(21)00312-3. · DOI
  115. Yu L, Yang R, Long Z, Tao Q, Liu B. Targeted therapy of non-small cell lung cancer: mechanisms and clinical trials. Front Oncol. 2024;14:1451230. https://doi.org/10.3389/fonc.2024.1451230. · DOI
  116. Hardavella G, Magouliotis DE, Chalela R, Januszewski A, Dennstaedt F, Putora PM, et al. Stage I and II nonsmall cell lung cancer treatment options. Breathe (Sheff). 2024;20(2): 230219. https://doi.org/10.1183/20734735.0219-2023. · DOI
  117. Sahoo D, Deb P, Basu T, Bardhan S, Patra S, Sukul PK. Advancements in platinum-based anticancer drug development: A comprehensive review of strategies, discoveries, and future perspectives. Bioorg Med Chem. 2024;112: 117894. https://doi.org/10.1016/j.bmc.2024.117894. · DOI
  118. Jiang P, Wu X, Wang X, Huang W, Feng Q. NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells. Oncotarget. 2016;7(28):43337–51. https://doi.org/10.18632/oncotarget.9712. · DOI
  119. Kim ES, Tang X, Peterson DR, Kilari D, Chow CW, Fujimoto J, et al. Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer. Lung Cancer. 2014;85(1):88–93. https://doi.org/10.1016/j.lungcan.2014.04.005. · DOI
  120. Sone K, Oguri T, Uemura T, Takeuchi A, Fukuda S, Takakuwa O, et al. Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort. BMC Cancer. 2019;19(1):246. https://doi.org/10.1186/s12885-019-5438-2. · DOI
  121. Paramasivan P, Kumar JD, Baskaran R, Weng CF, Padma VV. Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation. Cancer Drug Resist. 2020;3(3):647–65. https://doi.org/10.20517/cdr.2019.115. · DOI
  122. Nakagawa T, Inoue Y, Kodama H, Yamazaki H, Kawai K, Suemizu H, et al. Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) correlates with cisplatin resistance in human non-small cell lung cancer xenografts. Oncol Rep. 2008;20(2):265–70.
  123. Zhang Y, Chen Y, Huang W, Zhou Y, Wang Y, Fu K, et al. NPAS2 dampens chemo-sensitivity of lung adenocarcinoma cells by enhancing DNA damage repair. Cell Death Dis. 2024;15(1):101. https://doi.org/10.1038/s41419-023-06256-3. · DOI
  124. Weaver DA, Crawford EL, Warner KA, Elkhairi F, Khuder SA, Willey JC. ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines. Mol Cancer. 2005;4(1):18. https://doi.org/10.1186/1476-4598-4-18. · DOI
  125. Shen W, Qiu Y, Li J, Wu C, Liu Z, Zhang X, et al. IL-25 promotes cisplatin resistance of lung cancer cells by activating NF-κB signaling pathway to increase of major vault protein. Cancer Med. 2019;8(7):3491–501. https://doi.org/10.1002/cam4.2213. · DOI
  126. Qiu T, Zhou L, Wang T, Xu J, Wang J, Chen W, et al. miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2. Int J Mol Med. 2013;32(3):593–8. https://doi.org/10.3892/ijmm.2013.1439. · DOI
  127. Michels J, Obrist F, Vitale I, Lissa D, Garcia P, Behnam-Motlagh P, et al. MCL-1 dependency of cisplatin-resistant cancer cells. Biochem Pharmacol. 2014;92(1):55–61. https://doi.org/10.1016/j.bcp.2014.07.029. · DOI
  128. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113–25. https://doi.org/10.1056/NEJMoa1713137. · DOI · Paper page
  129. Chhouri H, Alexandre D, Grumolato L. Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer. Cancers (Basel). 2023;15(2). https://doi.org/10.3390/cancers15020504. · DOI
  130. Vasconcelos P, Gergis C, Viray H, Varkaris A, Fujii M, Rangachari D et al. EGFR-A763_Y764insFQEA Is a Unique Exon 20 Insertion Mutation That Displays Sensitivity to Approved and In-Development Lung Cancer EGFR Tyrosine Kinase Inhibitors. JTO Clin Res Rep. 2020;1(3). https://doi.org/10.1016/j.jtocrr.2020.100051. · DOI
  131. Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, et al. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018;4(11):1527–34. https://doi.org/10.1001/jamaoncol.2018.2969. · DOI · Paper page
  132. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015;21(6):560–2. https://doi.org/10.1038/nm.3854. · DOI · Paper page
  133. Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013;31(27):3335–41. https://doi.org/10.1200/jco.2012.45.0981. · DOI · Paper page
  134. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52. https://doi.org/10.1038/35021093. · DOI
  135. Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):61. https://doi.org/10.1186/s13058-020-01296-5. · DOI
  136. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74. https://doi.org/10.1073/pnas.191367098. · DOI
  137. AlFakeeh A, Brezden-Masley C. Overcoming endocrine resistance in hormone receptor-positive breast cancer. Curr Oncol. 2018;25(Suppl 1):S18–s27. https://doi.org/10.3747/co.25.3752. · DOI
  138. Brufsky AM, Dickler MN. Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance. Oncologist. 2018;23(5):528–39. https://doi.org/10.1634/theoncologist.2017-0423. · DOI
  139. Belachew EB, Sewasew DT. Corrigendum: Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer. Front Endocrinol (Lausanne). 2021;12: 689705. https://doi.org/10.3389/fendo.2021.689705. · DOI
  140. Willman M, Willman J, Lucke-Wold B. Endocrine resistant breast cancer: brain metastasis. Explor Target Antitumor Ther. 2022;3(2):240–51. https://doi.org/10.37349/etat.2022.00081. · DOI
  141. Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439–45. https://doi.org/10.1038/ng.2822. · DOI
  142. Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20(7):1757–67. https://doi.org/10.1158/1078-0432.Ccr-13-2332. · DOI · Paper page
  143. Katzenellenbogen JA, Mayne CG, Katzenellenbogen BS, Greene GL, Chandarlapaty S. Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance. Nat Rev Cancer. 2018;18(6):377–88. https://doi.org/10.1038/s41568-018-0001-z. · DOI
  144. Jeselsohn R, Bergholz JS, Pun M, Cornwell M, Liu W, Nardone A, et al. Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer Cell. 2018;33(2):173–86.e5. https://doi.org/10.1016/j.ccell.2018.01.004. · DOI
  145. Ferrando L, Vingiani A, Garuti A, Vernieri C, Belfiore A, Agnelli L, et al. ESR1 gene amplification and MAP3K mutations are selected during adjuvant endocrine therapies in relapsing Hormone Receptor-positive, HER2-negative breast cancer (HR+ HER2- BC). PLoS Genet. 2023;19(1): e1010563. https://doi.org/10.1371/journal.pgen.1010563. · DOI
  146. Lei JT, Shao J, Zhang J, Iglesia M, Chan DW, Cao J, et al. Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer. Cell Rep. 2018;24(6):1434–44.e7. https://doi.org/10.1016/j.celrep.2018.07.009. · DOI
  147. Li H, Prever L, Hirsch E, Gulluni F. Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer. Cancers (Basel). 2021;13(14). https://doi.org/10.3390/cancers13143517. · DOI
  148. Pearson A, Proszek P, Pascual J, Fribbens C, Shamsher MK, Kingston B, et al. Inactivating NF1 Mutations Are Enriched in Advanced Breast Cancer and Contribute to Endocrine Therapy Resistance. Clin Cancer Res. 2020;26(3):608–22. https://doi.org/10.1158/1078-0432.Ccr-18-4044. · DOI
  149. Sokol ES, Feng YX, Jin DX, Basudan A, Lee AV, Atkinson JM, et al. Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer. Ann Oncol. 2019;30(1):115–23. https://doi.org/10.1093/annonc/mdy497. · DOI
  150. Servetto A, Formisano L, Arteaga CL. FGFR signaling and endocrine resistance in breast cancer: Challenges for the clinical development of FGFR inhibitors. Biochim Biophys Acta Rev Cancer. 2021;1876(2): 188595. https://doi.org/10.1016/j.bbcan.2021.188595. · DOI
  151. Álvarez-Fernández M, Malumbres M. Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition. Cancer Cell. 2020;37(4):514–29. https://doi.org/10.1016/j.ccell.2020.03.010. · DOI
  152. Watt AC, Goel S. Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Breast Cancer Res. 2022;24(1):17. https://doi.org/10.1186/s13058-022-01510-6. · DOI
  153. Kim S, Armand J, Safonov A, Zhang M, Soni RK, Schwartz G, et al. Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer. Cell Rep. 2023;42(11): 113198. https://doi.org/10.1016/j.celrep.2023.113198. · DOI
  154. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82. https://doi.org/10.1126/science.3798106. · DOI · Paper page
  155. Derakhshani A, Rezaei Z, Safarpour H, Sabri M, Mir A, Sanati MA, et al. Overcoming trastuzumab resistance in HER2-positive breast cancer using combination therapy. J Cell Physiol. 2020;235(4):3142–56. https://doi.org/10.1002/jcp.29216. · DOI
  156. Cao Y, Li Y, Liu R, Zhou J, Wang K. Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer. Cancers (Basel). 2023;15(9). https://doi.org/10.3390/cancers15092568. · DOI
  157. Zuo WJ, Jiang YZ, Wang YJ, Xu XE, Hu X, Liu GY, et al. Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2-Targeted Therapies in Human Breast Cancer. Clin Cancer Res. 2016;22(19):4859–69. https://doi.org/10.1158/1078-0432.Ccr-15-3036. · DOI
  158. Kancha RK, von Bubnoff N, Bartosch N, Peschel C, Engh RA, Duyster J. Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib. PLoS ONE. 2011;6(10): e26760. https://doi.org/10.1371/journal.pone.0026760. · DOI
  159. Abraham J, Montero AJ, Jankowitz RC, Salkeni MA, Beumer JH, Kiesel BF, et al. Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10. J Clin Oncol. 2019;37(29):2601–9. https://doi.org/10.1200/jco.19.00858. · DOI
  160. Shokrollahi Barough M, Jalili N, Shafiee S, Salehi M, Naseri N, Javidi MA, et al. Anti-MUC1 nanobody can synergize the Tamoxifen and Herceptin effects on breast cancer cells by inducing ER, PR and HER2 overexpression. Int Immunopharmacol. 2023;124(Pt A): 110792. https://doi.org/10.1016/j.intimp.2023.110792. · DOI
  161. Sanz-Álvarez M, Martín-Aparicio E, Luque M, Zazo S, Martínez-Useros J, Eroles P et al. The Novel Oral mTORC1/2 Inhibitor TAK-228 Reverses Trastuzumab Resistance in HER2-Positive Breast Cancer Models. Cancers (Basel). 2021;13(11). https://doi.org/10.3390/cancers13112778. · DOI
  162. Autier P, Boniol M, La Vecchia C, Vatten L, Gavin A, Héry C, et al. Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database. BMJ. 2010;341: c3620. https://doi.org/10.1136/bmj.c3620. · DOI
  163. Yao Y, Chu Y, Xu B, Hu Q, Song Q. Risk factors for distant metastasis of patients with primary triple-negative breast cancer. Biosci Rep. 2019;39(6). https://doi.org/10.1042/bsr20190288. · DOI
  164. Arvandi S, Razmjoo S, Zaheri AP. Risk factors and survival of triple-negative breast cancer among breast cancer patients: Ten-year cross-sectional study in the southwestern Iranian population. Health Sci Rep. 2023;6(12): e1767. https://doi.org/10.1002/hsr2.1767. · DOI
  165. Birkbak NJ, Wang ZC, Kim JY, Eklund AC, Li Q, Tian R, et al. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents. Cancer Discov. 2012;2(4):366–75. https://doi.org/10.1158/2159-8290.Cd-11-0206. · DOI
  166. Naipal KA, Verkaik NS, Ameziane N, van Deurzen CH, Ter Brugge P, Meijers M, et al. Functional ex vivo assay to select homologous recombination-deficient breast tumors for PARP inhibitor treatment. Clin Cancer Res. 2014;20(18):4816–26. https://doi.org/10.1158/1078-0432.Ccr-14-0571. · DOI
  167. Tung NM, Boughey JC, Pierce LJ, Robson ME, Bedrosian I, Dietz JR, et al. Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline. J Clin Oncol. 2020;38(18):2080–106. https://doi.org/10.1200/jco.20.00299. · DOI
  168. Lehmann BD, Bauer JA, Schafer JM, Pendleton CS, Tang L, Johnson KC, et al. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors. Breast Cancer Res. 2014;16(4):406. https://doi.org/10.1186/s13058-014-0406-x. · DOI
  169. Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, et al. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat Rev. 2018;68:102–10. https://doi.org/10.1016/j.ctrv.2018.06.005. · DOI
  170. Pohl SG, Brook N, Agostino M, Arfuso F, Kumar AP, Dharmarajan A. Wnt signaling in triple-negative breast cancer. Oncogenesis. 2017;6(4): e310. https://doi.org/10.1038/oncsis.2017.14. · DOI
  171. Raith F, O'Donovan DH, Lemos C, Politz O, Haendler B. Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer Treatment. Int J Mol Sci. 2023;24(3). https://doi.org/10.3390/ijms24032289. · DOI
  172. Buyuk B, Jin S, Ye K. Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis. Cell Mol Bioeng. 2022;15(1):1–13. https://doi.org/10.1007/s12195-021-00694-9. · DOI
  173. Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, et al. NCCN guidelines insights: colon cancer, version 2.2018. J Natl Compr Canc Netw. 2018;16(4):359–69. https://doi.org/10.6004/jnccn.2018.0021. · DOI · Paper page
  174. Papke B, Azam SH, Feng AY, Gutierrez-Ford C, Huggins H, Pallan PS, et al. Silencing of Oncogenic KRAS by Mutant-Selective Small Interfering RNA. ACS Pharmacol Transl Sci. 2021;4(2):703–12. https://doi.org/10.1021/acsptsci.0c00165. · DOI · Paper page
  175. Xue JY, Zhao Y, Aronowitz J, Mai TT, Vides A, Qeriqi B, et al. Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition. Nature. 2020;577(7790):421–5. https://doi.org/10.1038/s41586-019-1884-x. · DOI · Paper page
  176. Park YL, Kim HP, Ock CY, Min DW, Kang JK, Lim YJ, et al. EMT-mediated regulation of CXCL1/5 for resistance to anti-EGFR therapy in colorectal cancer. Oncogene. 2022;41(14):2026–38. https://doi.org/10.1038/s41388-021-01920-4. · DOI
  177. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358(11):1160–74. https://doi.org/10.1056/NEJMra0707704. · DOI
  178. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29(15):2011–9. https://doi.org/10.1200/jco.2010.33.5091. · DOI · Paper page
  179. Van Emburgh BO, Sartore-Bianchi A, Di Nicolantonio F, Siena S, Bardelli A. Acquired resistance to EGFR-targeted therapies in colorectal cancer. Mol Oncol. 2014;8(6):1084–94. https://doi.org/10.1016/j.molonc.2014.05.003. · DOI
  180. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2023;41(18):3278–86. https://doi.org/10.1200/jco.22.02758. · DOI
  181. Therkildsen C, Bergmann TK, Henrichsen-Schnack T, Ladelund S, Nilbert M. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis. Acta Oncol. 2014;53(7):852–64. https://doi.org/10.3109/0284186x.2014.895036. · DOI
  182. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985–99. https://doi.org/10.1016/j.cell.2017.05.016. · DOI · Paper page
  183. Yang Y, Jiang H, Li W, Chen L, Zhu W, Xian Y, et al. FOXM1/DVL2/Snail axis drives metastasis and chemoresistance of colorectal cancer. Aging (Albany NY). 2020;12(23):24424–40. https://doi.org/10.18632/aging.202300. · DOI
  184. Kobayashi S, Yamada-Okabe H, Suzuki M, Natori O, Kato A, Matsubara K, et al. LGR5-positive colon cancer stem cells interconvert with drug-resistant LGR5-negative cells and are capable of tumor reconstitution. Stem Cells. 2012;30(12):2631–44. https://doi.org/10.1002/stem.1257. · DOI
  185. Bergengren O, Pekala KR, Matsoukas K, Fainberg J, Mungovan SF, Bratt O, et al. 2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review. Eur Urol. 2023;84(2):191–206. https://doi.org/10.1016/j.eururo.2023.04.021. · DOI
  186. Wong YN, Ferraldeschi R, Attard G, de Bono J. Evolution of androgen receptor targeted therapy for advanced prostate cancer. Nat Rev Clin Oncol. 2014;11(6):365–76. https://doi.org/10.1038/nrclinonc.2014.72. · DOI
  187. Desai K, McManus JM, Sharifi N. Hormonal Therapy for Prostate Cancer. Endocr Rev. 2021;42(3):354–73. https://doi.org/10.1210/endrev/bnab002. · DOI
  188. Koivisto P, Kononen J, Palmberg C, Tammela T, Hyytinen E, Isola J, et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 1997;57(2):314–9.
  189. Powell SM, Christiaens V, Voulgaraki D, Waxman J, Claessens F, Bevan CL. Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate. Endocr Relat Cancer. 2004;11(1):117–30. https://doi.org/10.1677/erc.0.0110117. · DOI
  190. Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332(21):1393–8. https://doi.org/10.1056/nejm199505253322101. · DOI
  191. Tan J, Sharief Y, Hamil KG, Gregory CW, Zang DY, Sar M, et al. Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol. 1997;11(4):450–9. https://doi.org/10.1210/mend.11.4.9906. · DOI
  192. Tien JC, Liu Z, Liao L, Wang F, Xu Y, Wu YL, et al. The steroid receptor coactivator-3 is required for the development of castration-resistant prostate cancer. Cancer Res. 2013;73(13):3997–4008. https://doi.org/10.1158/0008-5472.Can-12-3929. · DOI
  193. Andrieu C, Taieb D, Baylot V, Ettinger S, Soubeyran P, De-Thonel A, et al. Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E. Oncogene. 2010;29(13):1883–96. https://doi.org/10.1038/onc.2009.479. · DOI
  194. Le TK, Cherif C, Omabe K, Paris C, Lannes F, Audebert S, et al. DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer. Mol Ther. 2023;31(2):471–86. https://doi.org/10.1016/j.ymthe.2022.08.005. · DOI
  195. Aggarwal R, Huang J, Alumkal JJ, Zhang L, Feng FY, Thomas GV, et al. Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. 2018;36(24):2492–503. https://doi.org/10.1200/jco.2017.77.6880. · DOI · Paper page
  196. The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015;163(4):1011–25. https://doi.org/10.1016/j.cell.2015.10.025. · DOI
  197. Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016;22(3):298–305. https://doi.org/10.1038/nm.4045. · DOI
  198. Zhang W, Liu B, Wu W, Li L, Broom BM, Basourakos SP, et al. Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer. Clin Cancer Res. 2018;24(3):696–707. https://doi.org/10.1158/1078-0432.Ccr-17-1872. · DOI
  199. Zhao W, Lin ZX, Zhang ZQ. Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts. Cell Res. 2004;14(1):60–6. https://doi.org/10.1038/sj.cr.7290203. · DOI
  200. Tucci M, Bertaglia V, Vignani F, Buttigliero C, Fiori C, Porpiglia F, et al. Addition of Docetaxel to Androgen Deprivation Therapy for Patients with Hormone-sensitive Metastatic Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2016;69(4):563–73. https://doi.org/10.1016/j.eururo.2015.09.013. · DOI

200 of 237 shown

Cited by

Sorted by citations

Metadata

Authors
Gu, Y., Yang, R., Zhang, Y., Guo, M., Takehiro, K., Zhan, M., Yang, L., & Wang, H.
Venue
Molecular Biomedicine
Publisher
Springer Science and Business Media LLC
Published
2025-01-06
Volume
6
Issue
1
ISSN
2662-8651
DOI
10.1186/s43556-024-00239-2
PMC
PMC11700966
Cited by
184
References
20
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review