Abstract P6-11-05: Carnitine palmitoyltransferase 1A (CPT1A) mediates therapeutic response to endocrine therapy in estrogen receptor positive breast cancer

Abstract

Abstract Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related deaths in women in the United States, with more than 70% of the cases are hormone receptor positive (HR+) disease. Endocrine based therapies (ET) are successfully used, however, 30-50% will acquire ET resistance leading to tumor progression. Since the mechanism of acquired resistance remains unknown for ~60% of patients, identifying novel mechanisms of resistance is essential. We recently reported that carnitine palmitoyltransferase 1A (CPT1A), the rate limiting enzyme in fatty acid oxidation, is overexpressed in aggressive HR+ tumors, including ET resistant patients. We propose that CPT1A level and activity changes the tumor microenvironment to enhance tumorigenesis and contribute to ET resistance. To determine the mechanism by which CPT1A is promoting cell proliferation, tumor microenvironment, cellular signaling and ET resistance, we used a series of in vitro studies incorporating a panel of either endogenously or experimentally derived CPT1A-low and CPT1A-high controls, HR+ breast cancer cell lines as well as their ET resistant counterparts. We determined that CPT1A is upregulated in cell lines that acquire ET resistance. Our analyses demonstrated that levels of CPT1A can affect tumor formation ability in both CPT1A-high and adjacent CPT1A-low tumor cells with concurrent changes in both intra- and inter-cellular signaling which may be essential to promote tumor progression and mediate therapeutic response. This represents a promising step in understanding the mechanisms that promote tumorigenesis and ET resistance in HR+ breast cancer. Citation Format: Shaimaa Hussein, Michael L. Gatza, Shridar Ganesan. Carnitine palmitoyltransferase 1A (CPT1A) mediates therapeutic response to endocrine therapy in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-05.