SPORE in Skin Cancer

这是哈佛皮肤癌研究中心的竞争性更新申请，最初是在2001年10月资助的。这个孢子是设在布里格姆妇女医院，是达纳法伯哈佛癌症中心皮肤癌计划的一部分。该提案包括来自参与DFHCC的所有主要地点的研究人员，以及麻省理工学院的布罗德研究所。提出了七个转化研究项目。项目1旨在利用遗传学、基因组学和生物信息学工具为家族性黑色素瘤开发更精确和信息量更大的风险模型。项目2旨在将新的黑色素瘤癌基因组数据转化为预测和预后生物标志物，并确定作为药物开发靶点的新途径。项目3针对MITF，利用布罗德研究所强大的基因组和生物信息学资源来验证相关的生物标志物，并合理地识别该途径的新型抑制剂。项目4旨在探索黑色素瘤中癌症干细胞的存在，并将这些发现转化为预测，预后和治疗。项目5的重点是通过发现和靶向新化合物的协同途径来增强Braf抑制剂的适度临床治疗效果。项目6采用免疫抑制环境，通过靶向调节性T细胞，同时增强抗肿瘤免疫，阻碍晚期黑色素瘤患者的免疫治疗。项目7提出了针对晚期CTCL的靶向治疗，并寻求开发针对CCR4的治疗性人类抗体，CCR4是一种在这些细胞上忠实表达的趋化因子受体。这些项目由共享资源支持，包括生物统计学核心，组织和病理学核心以及管理，规划和评估核心。成功的发展项目和职业发展奖励计划构成了这个SPORE的重要组成部分，为转化性皮肤癌领域提供新的科学和人才。通过每个参与DFHCC的医院的大量补充机构承诺，促进了这项拟议的工作。

This is a competing renewal application for the Harvard SPORE in Skin Cancer, originally funded in October of 2001. This SPORE is based at Brigham and Women's Hospital and is part of the Skin Cancer Program of the Dana Farber Harvard Cancer Center. This proposal includes investigators from all major sites that participate in the DFHCC, as well as the Broad Institute of MIT. Seven translational research projects are proposed. Project 1 seeks to develop more precise and informative risk models for familial melanoma using genetic, genomic, and bioinformatic tools. Project 2 seeks to translate novel melanoma oncogenomic data into predictive and prognostic biomarkers and to identify novel pathways that are targets for drug development. Project 3 targets MITF, using the powerful genomic and bioinformatic resources of the Broad Institute to validate associated biomarkers and rationally identify novel inhibitors of this pathway. Project 4 seeks to explore the presence of cancer stem cells in melanoma, and to translate these findings to prediction, prognosis and therapy. Project 5 focuses on enhancing the modest clinical therapeutic effect of Braf inhibitors by discovering and targeting synergistic pathways with new compounds. Project 6 takes on the immunosuppressive milieu that thwarts immunotherapy in the advanced melanoma patients by targeting T regulatory cells while boosting antitumor immunity. Project 7 proposes targeted therapy for advanced CTCL, and seeks to develop therapeutic human antibodies to CCR4, a chemokine receptor faithfully expressed on these cells. These projects are supported by shared resources that include a Biostatistics Core, a Tissue and Pathology Core, and an Administration, Planning, and Evaluation Core. Successful Developmental Project and Career Development Award Programs constitute an important part of this SPORE, delivering new science and human talent to the translational skin cancer field. This proposed work is facilitated through substantial supplemental institutional commitments from each participating DFHCC hospital.