Mechanisms of TMZ resistance and potential therapeutic strategies
| Mechanisms of TMZ resistance | Markers or regulatory pathways | Potential therapeutic strategies |
|---|---|---|
| Insufficient intracellular concentration of TMZ | ||
| Extruded through an efflux pump | P-gp encoded MDR126,27 | Tariquidar44 |
| Extruded through a vesicle system | PTRF/Cavin-1 | Sequential therapy of TMZ followed by chloroquine28 |
| Aberrant DDR | ||
| MMR inactivation | MSH6 mutation30,31 | |
| BER hyperactivation | PARP-1/XRCC1 axis35 | Olaparib45 |
| Specific repair by MGMT | ||
| MGMT PARylation | PARP-mediated PARylation | Olaparib34 |
| Epigenetic regulation of MGMT | ATF3/p-p65/HADC1 axis | EPIC-041242 |