Table 2 Targeting autophagy for drug sensitivity in HCC
Molecular pathway | Drug | Remark | Refs |
|---|---|---|---|
m6A modification/FOXO3 | Sorafenib | Enhanced stability of FOXO3 by m6A modification in inducing autophagy and mediating chemoresistance | [232] |
HGF-MET | – | HFG- MET induces autophagy in mediating drug resistance Inhibition of HGF-MET and autophagy can reduce tumor progression and mediates drug sensitivity | [233] |
Hypoxia/FOXO3a | Sorafenib | Hypoxia is able to increase the expression of FOXO3a in autophagy induction and mediate drug resistance | [234] |
HMGB1/AMPK/mTOR | Doxorubicin | HMGB1 increases AMPK expression and inhibits mTOR Autophagy induction Doxorubicin resistance | [235] |
Osteopontin/FoxO3/autophagy | Epirubicin Cisplatin | Osteopontin increases FoxO3 stability in autophagy induction and mediation of drug resistance | [236] |
– | Oxaliplatin | Tumor-associated macrophages induce autophagy and inhibit apoptosis in mediating drug resistance | [237] |
miR-26b/USP9X/p53/autophagy | Doxorubicin | miR-26b reduces USP9X expression to prevent p53 degradation in autophagy inhibition and desensitization to doxorubicin chemotherapy | [238] |
SNHG16/miR-23b-3p/EGF1 | Sorafenib | SNHG16 increases EGF1 expression via inhibition of miR-23b-3p in autophagy induction and apoptosis inhibition, leading to the development of drug resistance | [239] |
Egr-1 | – | Upregulation of Egr-1 during hypoxia and its positive association with autophagy in triggering chemoresistance | [240] |
miR-21/PTEN/Akt | Sorafenib | miR-21 increases Akt expression by inhibiting PTEN signaling Inhibition of autophagy Development of drug resistance | [241] |
cFLIP/ER stress | Sorafenib | Silencing of cFLIP impairs drug resistance by preventing ER stress-mediated autophagy | [242] |
Beclin-1 | KU-0063794 | Silencing of Beclin-1 suppresses autophagy and increases drug sensitivity | [243] |
CD13/p38/Hsp27/CREB/ATG7 | 5-flourouracil | CD13 increases ATG7 expression via the p38/Hsp27/CREB axis, which induces chemoresistance | [244] |
miR-23b-3p/ATG12 | Sorafenib | miR-23b-3p reduces ATG12 expression, impairing autophagy and reversing sorafenib resistance | [245] |
p57/autophagy | EGFR inhibitors | p57 induces autophagy and enhances the potential of EGFR inhibitors in combating HCC | [246] |
VRK2 | JNK1/MAPK8/Bcl-2/Beclin-1 | VRK2 induces Beclin-1 expression via activation of the JNK1/MAPK8 axis to mediate dissociation of Bcl-2 from Beclin-1, triggering autophagy and mediating drug resistance | [247] |
Akt | Sorafenib | Suppression of Akt signaling reverses autophagy that promotes survival to autophagy that promotes death, thereby reversing drug resistance | [248] |
miR-101-3p/Beclin-1 | oxaliplatin | miR-101-3p reduces the expression of Beclin-1 in inhibiting autophagy and reversing drug resistance | [249] |
miR-651-3p/ATG3 | Cisplatin | miR-651-3p reduces ATG3 expression in suppressing autophagy and chemoresistance | [250] |