Abstract 5721: Dual targeting of CDK4/6 and CDK7 pathways augments tumor response in breast cancer

Abstract CDK7 plays a pivotal role in cell proliferation, serving as both a cell-cycle CDK regulator and a transcription machinery component. Clinical trials are currently exploring CDK7 inhibitors (CDK7i) as a second-line treatment for hormone receptor-positive (HR+) breast cancer post-CDK4/6 inhibitor (CDK4/6i) therapy progression and as a first-line treatment in triple-negative breast cancer (TNBC). This study evaluates the impact of CDK7i on transcription and CDKs activities and the synergistic potential of CDK7i in combination with CDK4/6i. Kinetic analyses indicate that CDK7i preferentially target global transcription over CDKs activities. Furthermore, a combination of CDK7i and CDK4/6i effectively suppresses cell proliferation in drug-naïve cells, albeit without the same efficacy in CDK4/6i-resistant cells. Our findings provide valuable insights into the evolving field of CDK inhibition strategies and provide critical guidance on the potential therapeutic application of CDK7i in breast cancer treatment. Citation Format: Eugene Son, Sungsoo Kim, Haram Park, Minah Kim, Hee Won Yang. Dual targeting of CDK4/6 and CDK7 pathways augments tumor response in breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5721.