Cellular Metabolism Contributes To Therapeutic Responses in BRAF-Mutated Melanomas

Abstract

Melanoma is the deadliest form of skin cancer, and virtually all patients progress on targeted therapies. Dysregulated metabolism has been shown to affect therapy response, so BRAF-mutated melanoma cell line models were used to connect cellular metabolism to therapeutic proliferative response. The data show that forcing a glycolytic metabolic strategy in the context of drug treatment enhances the antitumor effect. Anti-retrovirals, particularly zalcitabine, were shown to dramatically affect proliferation when combined with BRAF inhibitor. All in all, this dissertation provides an important contribution to response variability and assay development, the glycolytic biology in relation to BRAF inhibition, and a finer inspection of variability within a tumor.