Abstract 2120: Molecular characterization of cancer stem cells derived from drug-resistant melanoma

Abstract

Abstract BRAF kinase is a key intermediate in the MAP kinase pathway, which is associated with cell growth and proliferation. BRAFV600E activating mutation is found in 50-60% of all melanomas and 7% of all cancer malignancies. Despite an unprecedented initial response, patients treated with a highly effective BRAF inhibitor, vemurafenib (FDA approved 2011), can acquire drug resistance in as little as 6-9 months. Epigenetically driven epithelial-to-mesenchymal transition (EMT), a hallmark of cancer stem-like cells (CSCs), is a potential mechanism that melanomas employ to evade targeted therapy. We are investigating molecular alterations due to EMT in parental and vemurafenib-resistant melanoma sublines. Characterization of differential protein expression in parental and resistant cell lines through immunocytochemical, flow cytometric, and immunoblot analysis has indicated that EMT could confer drug resistance that prolongs survival of malignant melanomas. Furthermore, comparison of parental to isogenic resistant melanoma cell lines showed upregulated expression of EMT-related biomarkers that may be suggestive of the development of CSCs. These CSCs may serve as progenitor cells for therapy-resistant sublines in a heterogeneous melanoma population. Our research has identified notable EMT biomarkers in CSCs that can be used as novel targets for diagnosis and treatment of tumor resistance in melanoma patients. Citation Format: Elyse J. Berlinberg, William Crosson, Arbis Rojas, Ramin Nazarian. Molecular characterization of cancer stem cells derived from drug-resistant melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2120.