SPORE in Skin Cancer

这是哈佛大学皮肤癌孢子项目的一项竞争性续签申请，该项目最初是在10月份获得资助的 2001年。该孢子位于布里格姆妇女医院，是皮肤癌计划的一部分。 达纳·法伯哈佛癌症中心。这项提案包括来自所有主要地点的调查人员 参加DFCC，以及麻省理工学院博德学院。七个翻译研究项目是 建议。项目1寻求开发更精确和更有信息量的家族性黑色素瘤风险模型 遗传、基因组和生物信息学工具。项目2寻求翻译新的黑色素瘤癌基因组数据 转化为预测和预后的生物标志物，并识别作为药物靶点的新途径 发展。项目3以MITF为目标，利用布罗德强大的基因组和生物信息资源 验证相关的生物标记物并合理确定这一途径的新抑制剂。项目4 寻求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侧重于提高阿司匹林的适度临床疗效。 通过发现和靶向与新化合物的协同作用途径来开发BRAF抑制剂。项目6开始 通过靶向治疗阻碍晚期黑色素瘤患者免疫治疗的免疫抑制环境 T调节细胞，同时增强抗肿瘤免疫力。项目7建议对晚期患者进行靶向治疗 CTCL，并寻求开发针对CCR4的治疗性人源抗体，CCR4是趋化因子受体 在这些细胞上表达。这些项目得到了包括生物统计学在内的共享资源的支持 核心，组织和病理核心，以及管理、规划和评估核心。成功 发展项目和职业发展奖励计划是其中的重要组成部分 孢子，为转化性皮肤癌领域提供新的科学和人类人才。这项拟议的工作 通过每个参与DFCC的实质性补充机构承诺来促进 医院。

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 antibodie 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 Adminstration, Planning, and Evaluation Core. Successful Developmental Project and Career Development Awards Program 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.