Core A - Melanoma Biobank The propagation of human cancer cells has been a vital part of cancer biology including the seminal discovery of BRAF mutations in melanoma. Historically, cancer lines have proven to be a powerful system for screening novel therapeutic compounds and for isolating molecular determinants of sensitivity to anti-cancer drugs. The main charge of Core A- the Melanoma Biobank (MBB)- is to establish a critical set of melanoma cell lines from patients who undergo treatment with selective Braf inhibitors or other novel agents. Vital derivatives from Core A, along with annotated specimens, will be available to the rest of the P01 for molecular verification and functional validation of target candidates which may emerge from the various screens. The Specific Aims of Core A are (1) to provide a central source of melanoma cells obtained prior to initiation of selective Braf inhibitors (SBIs) and during relapse while undergoing treatment, (2) to provide mutational, copy number, expression and pathway actiyation profiles on cell lines and (3) to provide sensitivity data for selective BRAF inhibitors and other targeted therapies and to compare drug responses across various targeted agents and (4) to maintain a clinical database and tissue repository derived from patients on targeted therapy trials. This last Aim will leverage extant funding and will provide a critical piece of the correlative puzzle in the overall translational effort. By the end of the funded period, successful integration of all Projects and Cores within the POI will yield an unprecedented set of tissue specimens and vital cells adorned with meticulous clinical annotation and in-depth molecular profiling.