Chemoresistance refers to the ability of cancer cells to resist the effects of chemotherapy drugs, rendering treatments less effective or even ineffective. This resistance can be intrinsic (present before treatment) or acquired (developing during treatment) and poses a significant challenge in cancer therapy.
Eight recognized mechanisms underlying chemoresistance:
1.tumor heterogeneity;
2.inactivation of drugs (cytochrome P450, glutathione-S-transferase (GST), uridine diphospho-glucuronosyltransferase (UGT) superfamily);
3.overexpression of drug targets (EGFR and its downstream signaling targets);
4.efflux pump overexpression (MDR or P-gp, MRP1, ABCG2);
5.DNA damage repair;
6.evasion of cell death mediated by Bcl-2, Akt, NF-κB and STAT;
7.EMT favored by overexpression of TGF-β, FAK VEGF; and
8.epigenetic changes.
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