Preventing and Overcoming Resistance to PARP Inhibitors: A Focus on the Clinical Landscape

Cancers

Josep V. Forment¹  Elsa Irving¹  Rosario Prados-Carvajal¹  Natalia Lukashchuk² 

[1] DDR Biology, Bioscience, Oncology R&D, AstraZeneca, Cambridge CB4 0WG, UK;Translational Medicine, Oncology R&D, AstraZeneca, Cambridge CB4 0WG, UK;

关键词: PARP inhibitor (PARPi);    resistance;    homologous recombination repair (HRR);    molecular mechanisms;    clinical relevance;   

DOI  :  10.3390/cancers14010044

来源: DOAJ

【 摘 要 】

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are now a first-line maintenance treatment in ovarian cancer and have been approved in other cancer types, including breast, pancreatic and prostate. Despite their efficacy, and as is the case for other targeted therapies, resistance to PARPi has been reported clinically and is generating a growing patient population of unmet clinical need. Here, we discuss the mechanisms of resistance that have been described in pre-clinical models and focus on those that have been already identified in the clinic, highlighting the key challenges to fully characterise the clinical landscape of PARPi resistance and proposing ways of preventing and overcoming it.

【 授权许可】

Unknown