The MYC oncogene is highly amplified in many human cancers, and importantly is frequently amplified in ovarian cancer. It encodes a helix-loop-helix transcription factor, Myc, that dimerizes with a partner, Max, to bind the DNA consensus E-box sequence and broadly affects transcription by alleviating RNA polymerase pausing. Myc activates hundreds to thousands of genes that involve ribosome biogenesis, metabolism, and cell cycle control. Its deregulated expression in cancer cells causes a constitutive drive for cell growth, thereby rendering MYC-overexpressing cells addicted to specific metabolic pathways that may be dependent on the mutational spectrum of the cancer cell. For example, loss of p53 in combination with deregulated MYC, relieve cells from apoptotic pressure and unleash MYC's full potential as an oncogenic transcription factor. The dependence of MYC-overexpressing cells on nutrients provide a synthetic lethal approach to target metabolism for therapy. Further, deregulated MYC disrupt the circadian clock and metabolism in favor of cell growth-related metabolism. Hence, timing of metabolic therapies for MYC-induced cancers such as ovarian cancer may provide a new therapeutic window for emerging metabolic therapies.
Note: This abstract was not presented at the conference.
Citation Format: Chi Van Dang. Myc, metabolism, and cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA13.