Table 1.
Drug resistance mechanisms of breast cancer
| Drug resistance | Drugs | Mechanism | Reference |
|---|---|---|---|
| Chemotherapy | DNA damage agents | A feedback loop between MORC2 and PARP1 facilitates efficient DNA repair | 48 |
| NAT10-mediated MORC2 acetylation contributes to DNA damage-induced G2 checkpoint activation | 49 | ||
| Rac1 promotes the glycolysis, especially non-oxidative pentose phosphate pathway and nucleoside metabolism | 50 | ||
| 5-FU | A feed-forward circuit between SRGN and YAP induces HDAC2 expression to maintain stemness and chemoresistance | 51 | |
| adriamycin | GSTP1 promotes autophagy by interacting with PI3K, p110α, and then preventing PI3K-Akt-mTOR pathway signaling | 52 | |
| paclitaxel | SYTL4 decreases microtubule stability via inhibiting microtubule polymerization | 53 | |
| EGOT enhances autophagosome accumulation via the upregulation of ITPR1 expression in cis and in trans | 54 | ||
| MITR increases IL11 expression and activation of downstream JAK/STAT3 signaling pathway | 55 | ||
| Endocrine therapy | tamoxifen/fulvestrant | Estrogen receptor antagonists stabilize MORC2 via the GPER1-PRKACA-CMA pathway | 56 |
| UCH-L1 contributes to loss or reduction of ERα by the deubiquitinase-mediated stability of EGFR | 62 | ||
| tamoxifen | BDNF-AS promotes RNH1 degradation via TRIM21-mediated ubiquitination and sustains the activation of mTOR signaling | 57 | |
| DILA1 blocks phosphorylation and degradation of Cyclin D1 | 58 | ||
| Ajuba/DBC1/CBP/p300 ternary complex co-activates ERα transcriptional activity and enhances ERα acetylation | 59 | ||
| miR-575 enhances ERα activity by targeting CDKN1B and BRCA1 | 60 | ||
| fulvestrant | Inactivation of neddylation with MLN4924 inhibits ERα via delaying SGK degradation and inducing FOXO3a nuclear export | 61 | |
| Targeted therapy | trastuzumab | TINCR promotes HER-2 expression by sponging miR-125b and promotes EMT by targeting Snail-1 | 63 |
| palbociclib | TROJAN binds to NKRF and inhibits its interaction with RELA, upregulating the expression of CDK2 | 64 | |
| olaparib | ATRA sensitizes BRCA1-proficient breast cancer to PARP inhibition by inhibiting Pin1 and destabilizing BRCA1 | 65 | |
| Immunotherapy | anti-PD-1 | Low-dose VEGFR2 blockade sensitizes tumors to anti-PD-1 therapy via upregulation of PD-1 on immune cells through stimulating the secretion of OPN and TGF-β |
67 |
| anti-PD-L1 | PARP1 suppresses PD-L1 transcription through interacting with NPM1 and abolishing the binding of NPM1 at the PD-L1 promoter | 68 | |
| anti-PD-1/anti-PD-L1 | TNC contributes to autophagy deficiencymediated immunosuppression via suppressing LC3B and CD8+ T cells | 69 |
PRKACA protein kinase cAMP-activated catalytic subunit alpha, CMA chaperone-mediated autophagy, SGK serum and glucocorticoid-induced protein kinase, FOXO3a forkhead box O3a, OPN osteopontin.