Figure 2.

Overlapping mechanisms of resistance to Platinum and PARP-inhibitor treatment. Platinum and PARPi demonstrate distinct and overlapping mechanisms of acquired treatment resistance. Whilst both demonstrate reactivation of HRR and loss of 53BP1, and replication fork protection promoting progression through the cell cycle, platinum resistance is additionally associated with defects in the NER pathway, including increased ERCC1 activity. Reduced intracellular drug accumulation is achieved via copper transporters for platinum, and MDR1 drug efflux pump for PARPi. In both instances, an immunosuppressive microenvironment and desmoplastic stroma likely contribute to tumour progression. Abbreviations; HRR, homologous recombination repair, MDR1, Multidrug Resistance Protein 1, ERCC1, DNA excision repair protein ERCC-1, PARPi, PARP inhibitor.