Abstract A03: Integrative analyses reveal distinct metabolic dysregulation in MYC-driven, basal breast cancer

Abstract

Abstract Dysregulated metabolism is a hallmark of all human cancers. The observation that tumors display unique changes in metabolism led to the hypothesis that tumors may be dependent upon an altered metabolic state. c-MYC (MYC) is a proto-oncogene and transcription factor activated in many cancers that regulates multiple metabolic pathways. Our lab and others have shown that MYC is activated in a large proportion of basal-like breast cancer, the most aggressive subtype of human breast cancer. However, the role of MYC in basal breast cancer metabolism is largely unknown. No efficacious MYC inhibitor is available for clinical use, however, an alternative treatment strategy is to target cellular pathways required in the context of MYC activation. We hypothesize that basal-like breast cancer harbors distinct, MYC-driven metabolic dysregulation, and that this dysregulation can be targeted therapeutically to induce MYC-dependent synthetic lethality. Utilizing in vitro and in vivo models of MYC-driven and basal breast cancer, including patient-derived cell lines and patient-derived xenograft mouse tumor models, we have performed metabolomic and transcriptomic analyses. We investigate MYC-dependent metabolic dysregulation via integrated analyses of these datasets, and find distinct changes that could reveal essential metabolic pathways for MYC-driven, basal tumorigenesis. Citation Format: Roman Camarda, Sanjeev Balakrishnan, Alicia Y. Zhou, Brittany Anderton, Henok Eyob, Rebecca Kohnz, Daniel K. Nomura, Andrei Goga. Integrative analyses reveal distinct metabolic dysregulation in MYC-driven, basal breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A03.