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Table 6 Mechanisms of resistance to PARP inhibitors

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

  1. HR Homologous recombination. For further details refer to text and [83–85]