The University of Texas M. D. Anderson Cancer Center SPORE in Ovarian Cancer

德克萨斯大学安德森癌症中心（MDACC） SPORE的总体目标是通过基于卵巢癌的分子、细胞和临床生物学的检测和治疗方面的创新转化研究，降低卵巢癌的发病率和死亡率。IVIDACC拥有一个独特的社区，由35名有才华的研究人员组成，他们致力于卵巢癌的转化、临床、基础和基于人群的研究，其中20人直接参与了SPORE。合作者包括来自9所大学和4家公司的25名研究人员。在过去的4年里，IVIDACC已经治疗了1055名新的卵巢癌和腹膜癌患者，并将241名患者进行了临床试验。MDACC通过招聘、薪酬支持、临床设施、实验室空间和慈善基金高度重视卵巢癌研究。在SPORE的帮助下，MDACC招募了5名对卵巢癌研究感兴趣的优秀教师，加强了研究基础设施，资助了13个发展研究项目（DRP），并支持了4名职业发展计划（DRP）获奖者。在过去的5年里，《孢子》的研究人员发表了381篇关于卵巢癌的同行评议出版物。成果包括：1)制定了早期卵巢癌的两阶段筛查策略，为发现早期疾病提供了30%的阳性预测值；2)鉴定出一组可检测87%早期卵巢癌的生物标志物；2)发现周细胞作为抗血管生成治疗的靶点；3) afliberept （VEGF-Trap）联合多西他赛治疗铂耐药疾病的有效率为39%；4) PTEN突变卵巢癌患者对AKT抑制剂perifosine的应答检测；5)发现多达30%的卵巢癌患者存在BRCA功能障碍；6)确定PVT-1和PFDN4作为siRNA治疗的靶点。下一个资助期的五个项目将：1)评估用于卵巢癌早期检测的多标记算法；2)靶向Dll4/Notch信号逆转耐药并协同抗vegf治疗；3)通过抑制MEK、AKT和IGFR对低度恶性肿瘤进行个体化治疗；4)对PI3K信号激活或BRCA功能障碍的高级别卵巢癌进行个性化治疗；5)在临床前和临床研究中，发展间充质干细胞作为IFN-B向肿瘤输送的载体。这项工作将得到三个核心的支持：行政；生物统计学、生物信息学和系统生物学；和病理。将为DRP和CDP受助人提供支持，以获得同行评审的资金。内部、外部和维权顾问将继续提供宝贵的建议。

The overall goal of the University of Texas M. D. Anderson Cancer Center (MDACC) SPORE is to reduce the morbidity and mortality of ovarian cancer through innovative translational research in the detection and treatment of ovarian cancer based upon the molecular, cellular and clinical biology of the disease. IVIDACC contains a unique community of >35 talented investigators who are dedicated to translational, clinical, fundamental and population-based ovarian cancer research, 20 of whom participate directly in the SPORE. Collaborators include 25 investigators from 9 universities and 4 companies. Over the last 4 years IVIDACC has cared for 1,055 new patients with ovarian and peritoneal cancer and have placed 241 on clinical trials. MDACC has given high priority to ovarian cancer research through recruitment, salary support, clinical facilities, laboratory space and philanthropic funds. MDACC with the help of the SPORE has recruited 5 outstanding faculty members with an interest in ovarian cancer research, strengthened the research infrastructure, funded 13 developmental research projects (DRP) and supported 4 career development program (DRP) awardees. Over the last 5 years SPORE investigators have contributed 381 peer-reviewed publications regarding ovarian cancer. Achievements include: 1) development of a two-stage screening strategy for early ovarian cancer that has provided a 30% positive predictive value for detecting early stage disease; 2) identification of a panel of biomarkers that detect 87% of early stage ovarian cancers; 2) discovery of pericytes as targets for anti-angiogenic therapy; 3) observation of a 39% response rate with aflibercept (VEGF-Trap) and docetaxel against platinum-resistant disease; 4) detection of response to the AKT inhibitor perifosine in ovarian cancers with PTEN mutations; 5) discovery that as many as 30% of ovarian cancer patients have BRCA dysfunction; and 6) identification of PVT-1 and PFDN4 as targets for siRNA therapy. Five project proposed for the next grant period will: 1) evaluate a multi-marker algorithm for early detection of ovarian cancer; 2) target Dll4/Notch signaling to reverse resistance and synergize with anti-VEGF therapy; 3) test personalized therapy of low grade cancer with MEK, AKT and IGFR inhibition; 4) personalize treatment for high grade ovarian cancers with activated PI3K signaling or BRCA dysfunction; and 5) develop mesenchymal stem cells as vehicles for tumor tropic delivery of IFN-B in preclinical and clinical studies. This work will be supported by three cores: Administrative; Biostatistics, Bioinformatics and Systems Biology; and Pathology. Support will be provided for DRP and CDP recipients to attain peer-reviewed funding. Valuable advice will continue to be provided by internal, external and advocate advisors.