A Novel BET Inhibitor for Breast Cancer Combination Therapy

Type of Award: accelerator
Award Number: A-009
Award Period: January 2019 - December 2019
Amount Awarded: $ 100,000.00
PI(s): Gregory Thatcher, UIC;

Abstract: Deregulation of epigenetic processes is one of the hallmarks of cancer. Bromodomain-containing proteins are key epigenetic regulators: among 61 bromodomains, the bromodomain and extra- terminal (BET) family has been targeted by inhibitors in cancer clinical trials. We have designed a novel, potent, selective BET inhibitor, YF-2-23, with superiority to many inhibitors in clinical trials, when tested in breast cancer cell lines. Although YF-2-23 may have use in multiple cancers, a persuasive argument exists for pursuing combination therapy in drug-resistant ER+ breast cancer, with a novel, proprietary, orally bioavailable selective estrogen receptor degrader (SERD). We propose to obtain crucial preclinical efficacy data on the YF-2-23 combination in xenograft models of metastatic ER+ breast cancer, resistant to endocrine therapy and CDK4/6 inhibitors.