Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE

描述（由申请人提供）：本卵巢癌卓越研究专业项目（SPORE）由丹娜-法伯/哈佛癌症中心（DF/HCC）提交，包括5个转化项目，3个支持核心项目和2个协同项目。项目1将结合护士健康队列和大型病例对照研究的数据，研究影响可改变暴露的基因-环境相互作用，如消炎药或生殖器滑石粉的使用。项目2旨在利用创新的基于dna的技术与生物信息学相结合，在大型和特征明确的早期肿瘤集合中识别组织学特异性分子遗传变化。项目3将通过对参加DF/HCC和癌症遗传网络诊所进行预防性输卵管卵巢切除术的妇女的术前和术后血液和尿液标本进行蛋白质组学分析，确定隐匿性卵巢癌或前驱病变的生物标志物。项目4将确定与紫杉醇和卡铂耐药相关的遗传途径，建立在令人兴奋的细胞系研究基础上，指出获得性途径和转录谱，寻求确定内在机制。项目5提出I期和II期试验，以评估两种不同疫苗方法的价值——一种使用重组痘苗病毒，另一种涉及树突状细胞和卵巢癌细胞融合。项目1和3满足与预防或筛选相关的孢子要求，而项目2、4和5解决可能转化为干预策略的生物学基础。行政、生物统计和组织核心是协同构建的，将支持当前和未来项目的目标。发展研究计划将加强DF/HCC卵巢癌孢子的科学和技术基础，并保持其项目的平衡和多样性，而互补的职业发展计划将增加致力于卵巢癌的研究人员的数量，并最大限度地发挥他们成为领导者的潜力。DF/HCC孢子的总体任务是解决卵巢癌的全面预防、早期发现和治疗。

DESCRIPTION (provided by applicant): This Specialized Program of Research Excellence (SPORE) in Ovarian Cancer is submitted from the Dana-Farber/Harvard Cancer Center (DF/HCC) and combines 5 translational projects, 3 supportive cores, and 2 synergistic programs. Project 1 will examine gene-environmental interactions affecting modifiable exposures, such as anti-inflammatory drug or genital talc use, in combined data from the Nurses' Health Cohort and a large case-control study. Project 2 seeks to identify histology-specific molecular genetic changes in large and well-characterized collections of early-staged tumors using innovative DNA-based technologies coupled with bioinformatics. Project 3 will identify biomarkers of occult ovarian cancers or precursor lesions through proteomic analysis of pre- and post-operative blood and urine specimens from women attending DF/HCC and Cancer Genetics Network Clinics for prophylactic salpingo-oophorectomy. Project 4 will identify genetic pathways associated with paclitaxel and carboplatin drug resistance, building upon exciting cell line work that points towards acquired pathways and transcriptional profiling that seeks to identify intrinsic mechanisms. Project 5 proposes Phase I and II trials to assess the value of two distinct vaccine approaches---one using recombinant vaccinia viruses and another involving dendritic cell and ovarian cancer cell fusions. Projects 1 and 3 satisfy SPORE requirements related to prevention or screening while Projects 2, 4, and 5 address biologic foundations that may translate into interventional strategies. Administrative, Biostatistical, and Tissue Cores are collaboratively structured and will support the aims of current and future projects. A Developmental Research Program will reinforce scientific and technological foundations for the DF/HCC Ovarian Cancer SPORE and maintain the balance and diversity of its projects, while a complementary Career Development Program will increase the number of researchers committed to ovarian cancer and maximize their potential to be leaders. The overall mission of the DF/HCC SPORE is to address the full range of prevention, early detection, and treatment of ovarian cancer.