Abstract

Kinetics of Cellular De-differentiation Transition in Metastatic Melanoma

Wei Wei, Assistant Professor, Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine

Targeted therapies blocking BRAF and MEK have demonstrated high rates of responses. However, after an initial tumor regression, almost all BRAF-mutant melanoma tumors acquire resistance against BRAF inhibitors, but with highly variable kinetics. The general relationship between the phenotypic transition and drug-induced adaptation is not well known. Further, the detailed kinetics of the transition, especially at the early stage of treatment when the cancer cells are beginning to adapt to the drug, is also not clear. I will talk about how to harness single cell proteomic methods, bulk transcriptomic profiling, and mathematical modeling, to investigate the kinetics of the phenotypic adaptation of a panel of BRAFV600 mutated patient-derived melanoma cell lines and patient biopsies upon BRAF inhibition, with an eye towards identifying strategies for halting the adaptive response so as to lead to prolonged tumor growth inhibition.