Abstract
Abstract Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of key mediators of DNA repair and replication beyond PARP, such as ATR and WEE1. Dr Yap will cover the latest advances in biomarker-driven synthetic lethal combination treatment strategies for different cancers. He will discuss efforts to optimize combination therapies that are ongoing across a range of cancers, involving the development of predictive biomarkers of response, assessment of the mechanisms underlying resistance, and the evaluation of rational, tolerable combinations with novel molecularly targeted agents, immune-checkpoint inhibitors and antibody drug conjugates. Citation Format: Timothy A. Yap. Overcoming PARP inhibitor resistance through rational combinations in the clinic. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY32-03.
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