Abstract PO-051: Metabolic alterations reveal epigenetic vulnerabilities in breast cancer

Tumor progression and therapeutic resistance in cancer are characterized by changes in cell identity, which is regulated in part by the epigenetic landscape of the cells. Alterations in metabolic profiles can contribute to changes in cell fate during tumor progression through remodelling of chromatin landscapes. We show that chemoresistance in triple-negative breast cancer is characterized by altered cellular metabolism, impacting the levels of metabolites required for DNA and histone methylation. Using models of chemotherapy resistance breast cancer, we have identified metabolic and epigenetic dependencies specific to drug-resistant breast cancer cells. We show that the remodelling of epigenetic states upon chemotherapy-induced metabolic stress can contribute to drug resistance in breast cancer cells by enabling the maintenance of transposable element repression and preventing the induction of cytotoxic stress-induced viral mimicry. While these metabolic and epigenetic changes contribute to the enhanced tumorigenic fitness of chemo resistant breast cancer, they reveal epigenetic vulnerabilities that can be therapeutically targeted in drug-resistant tumors.

Citation Format: Genevieve Deblois. Metabolic alterations reveal epigenetic vulnerabilities in breast cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-051.