From: PARP inhibitors in the management of breast cancer: current data and future prospects
Mechanism of resistance | Proposed explanation | HR restoration |
---|---|---|
Restoration of BRCA functionality | Secondary mutation in BRCA1/2 | Potentially complete |
DNA damage repair rewiring | Mutations in p53 binding protein 1 | Partial |
Increased drug efflux | Overexpression of P-glycoprotein | None |
Increased activity of BRCA1/2 proteins | Increased stimulation of hypomorphic BRCA1/2 protein expression | Partial |
Decreased PARP expression | Epigenetic silencing or increased turnover | None |