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Utilizing Systems Level Approaches To Identify Key Mechanisms Of Drug Resistance In Braf Mutated Melanoma, Kim H.T. Paraiso

USF Tampa Graduate Theses and Dissertations

In the last four years, seven new drugs have been FDA approved for the treatment of late stage melanoma, for the field of melanoma, this marks an incredibly exciting. Three of these new therapies, vemurafenib, dabrafenib and trametinib are small molecule kinase inhibitors that target the MAPK pathway and as such have been approved for the treatment of BRAFV600 mutant melanomas. Yet despite recent advances, mechanisms of intrinsic and acquired BRAF inhibitor resistance continue to undermine uniform and long-lasting therapeutic responses. Several studies have shown that the reactivation of MAPK signaling is a critical event leading to BRAF inhibitor resistance. …