CORE B ABSTRACT Recent advances in the treatment of metastatic melanoma with targeted therapies are highly successful initially but are ultimately limited by the development of tumor resistance. On the other hand, checkpoint inhibitors are associated with durable responses but only benefit a minority of patients.
The aims of all of the projects in this application are to understand the mechanisms and develop strategies to overcome resistance to both combined targeted therapies and checkpoint inhibitor immunotherapies in melanoma. The proposed studies require an efficient Biospecimen Core that can provide a variety of high quality biospecimens to the investigators.
The specific aims of the Biospecimen Repository and Processing Core (BRPC - Core B) of the PPG are to: 1 ) Centralize performance of specialized pathology services, including biosample (tissue and biofluid) storage, tracking, distribution and analysis; 2) Provide well-characterized melanoma tissues, cell lines and short-term cultures from patients enrolled on combination therapies and treated with BRAF/MEK inhibitors or checkpoint inhibitors and prospectively develop additional cell lines; and 3) Develop techniques to better characterize cells from within the tumor microenvironment for more sophisticated analysis in situ and at the single cell level. BRPC provide the advanced expertise in melanoma biology, cell line development, pathologic interpretation and biorepository management that is required by all proposed studies.
The proposed projects of this PPG seek to understand the molecular and cellular basis for mechanisms and resistance to targeted therapy or checkpoint inhibitors to allow the rational design of combinatorial therapies that treat and eventually prevent resistance. These studies rely heavily on patient-derived samples collected both at UCLA and provided by outside collaborators through the Biospecimen Repository and Processing Core (BRPC). Core B will serve for obtention, generation, and authentication of biomaterial (tissue and biofluid) from patient samples; as well as provide advanced expertise in melanoma biology, cell line development, pathologic interpretation and biorepository management for all proposed studies.