Clinically Annotated Human Melanoma for TMEN Research

Flaherty博士是第一个目标组合的首席研究员 在单一药物BRAF抑制的基础上进行治疗试验，其中选择性MEK抑制剂与此相结合 探员。除了是这些临床试验方案的学术设计师外，Flaherty博士和他的同事们 在DF/HCC，这些试验中积累了最多的患者。因此，我们的中心不会 不仅拥有使用这些药物最长的临床经验，而且还拥有越来越大的 在治疗前和治疗期间以及在治疗期间获得的存档肿瘤标本和新鲜的肿瘤活检 临床进展时间。该中心将继续收集治疗前和治疗期间的肿瘤活检 使用BRAF抑制剂，然后鉴定和分离肿瘤微环境的细胞成分 包括免疫亚群、内皮细胞、周细胞和成纤维细胞。我们也会从基因上 表征肿瘤细胞以前描述的癌基因和肿瘤抑制基因的改变，包括 点突变和拷贝数。我们的团队独一无二地准备指导我们的临床和研究 基础设施，以研究BRAF靶向治疗的耐药性问题。

Dr. Flaherty has been the principal investigator of the first combination targeted therapy trial to build on single agent BRAF inhibition in which a selective MEK inhibitor is combined with this agent. In addition to being the academic architect of these clinical trial protocols, Dr. Flaherty and colleagues at DF/HCC have accrued the largest number of patients to these trials. As a consequence, our center not only has the longest clinical experience with these agents, but also an increasingly large repository of archival tumor specimens and fresh tumor biopsies obtained before and during treatment, as well as at the time of clinical progression. This Core will continue to collect tumor biopsies prior to and during treatment with BRAF inhibitors, and then identify and isolate cellular constituents of the tumor microenvironment including immune subpopulations, endothelial cells, pericytes, and fibroblasts. We will also genetically characterize tumor cells for previously described oncogene and tumor suppressor gene alterations including point mutations and copy number. Our group is uniquely poised to direct our clinical and research infrastructure to studying the problem of resistance to BRAF targeted therapy.