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Dana Farber/Harvard Cancer Center Skin SPOREThomas S. Kupper, M.D. For more information on this specific SPORE’s institution, please visit: http://www.dfhcc.harvard.edu/spores/skin/ The DF/HCC SPORE in Skin Cancer has just been funded for an additional five years. The Skin SPORE includes investigators from BIDMC, BWH, CHMC, DFCI, MGH, and the Broad Institute of MIT. The SPORE is composed of five translational research projects, each based on discoveries made during the first funding period. In Project 1, investigators have identified candidate human melanoma stem cells, and will perform studies relevant to prognosis and therapy of human melanoma. Project 2 is based on two distinct transcriptional signatures identified human melanomas, one of which is characterized by high expression of Microphthalmia transcription factor (MITF). Using Gene Expression High-Throughput Screening, investigators will screen large compound libraries for activity against the MITF transcriptional signature in human melanomas, with the goal of developing new therapies. Project 3 stems from the observation that CTCL cells uniformly express the chemokine receptor CCR4. The investigators plan to develop further a lead candidate therapeutic antibody directed against huCCR4, now in hand. Project 4 evolves from observations that early and imperfect B-raf inhibitors are ineffective as single agents for advanced melanoma, even in BRAF* tumors. These investigators will explore the mechanism of this phenomenon, in part through an interSPORE trial of a new Braf inhibitor (RAF265), and will identify molecular pathways that suggest combination therapy. Project 5 will link population science to melanoma genetics and prognosis, using well annotated epidemiologic /clinical cohorts linked to archived pathology specimens, using a novel platform (DASL) that permits transcriptional profiling in FFPE samples. These projects are supported by a Biospecimen Access and Analysis Core, a Biostatistics and Bioinformatics Core, and an Administration, Evaluation, and Planning Core. Successful Developmental Project and Career Development Award Programs continue as important elements of this SPORE. We are confident that the translational science in this proposal will have an important impact on human skin cancer over the next five years.
SKIN PROJECTSProject 1: ABCB5 and Melanoma Stem Cells: Implications for Prognosis and Therapeutic Targeting Project 2: Molecular Signatures of Melanoma: Predicting Response to Therapy and Targeting the MITF Pathway Project 5: Correlating Environmental and Genetic Risk Factors with Molecular Signatures in Melanoma
CORESCore 1: Administration, Evaluation and Planning Core 2: Biostatistics and Bioinformatics Core 3: Biospecimen Access and Analysis Core |
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