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孢子在卵巢癌中的应用

• 批准号: 8540094
• 负责人: ROBERT C BAST
• 金额: $ 208.27万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8540094
• 关键词: Achievement; Advocate; Algorithms; Antibodies; Autoantibodies; Automobile Driving; Bioinformatics; Biological Markers; Biology; Biometry; CD44 gene; Cancer Center; Cancer Patient; Caring; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Communities; Detection; Development; Disease; Disease Resistance; Dose; Engraftment; Faculty; Functional disorder; Funding; Goals; Grant; Human; Hypoxia; Interferons; Lead; MAP Kinase Gene; MEK inhibition; MEKs; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Mesenchymal Stem Cells; Modeling; Molecular; Morbidity - disease rate; Mus; Mutation; Normal tissue morphology; Nuclear; Ovarian Carcinoma; Ovarian Serous Adenocarcinoma; PTEN gene; Pathology; Pathway interactions; Patients; Peer Review; Performance; Pericytes; Perifosine; Phase; Philanthropic Fund; Platinum; Postmenopause; Pre-Clinical Model; Predictive Value; Proteins; Proto-Oncogene Proteins c-akt; Publications; Recruitment Activity; Recurrence; Research Infrastructure; Research Personnel; Research Project Grants; Resistance; Risk; Role; Route; Screening for Ovarian Cancer; Series; Services; Signal Transduction; Small Interfering RNA; Specificity; Staging; Systems Biology; Testing; Time; Translational Research; Ultrasonography; Universities; University of Texas M D Anderson Cancer Center; VEGF Trap; Vascular Endothelial Growth Factors; Visit; WFDC2 gene; Wages; Woman; Work; Xenograft procedure; anticancer research; base; bevacizumab; cancer cell; cancer therapy; career development; docetaxel; human FRAP1 protein; imaging modality; improved; inhibitor/antagonist; innovation; interest; laboratory facility; mTOR Inhibitor; member; mortality; mutant; notch protein; operation; outcome forecast; peritoneal cancer; population based; pre-clinical; preclinical study; programs; response; screening; translational clinical trial; tumor

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.

德克萨斯大学M。D.安德森癌症中心（MDACC）SPORE旨在通过基于疾病的分子、细胞和临床生物学的创新转化研究来检测和治疗卵巢癌，从而降低卵巢癌的发病率和死亡率。IVIDACC包含一个由超过35名才华横溢的研究人员组成的独特社区，他们致力于转化，临床，基础和基于人群的卵巢癌研究，其中20人直接参与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已经照顾了1,055名卵巢癌和腹膜癌的新患者，并将241名患者置于临床试验中。 MDACC通过招聘、工资支持、临床设施、实验室空间和慈善基金高度重视卵巢癌研究。MDACC在SPORE的帮助下招募了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，SPORE研究人员贡献了381篇关于卵巢癌的同行评议出版物。取得的成就包括：1）开发早期卵巢癌的两阶段筛查策略，其为检测早期疾病提供了30%的阳性预测值; 2）鉴定一组生物标志物，其检测87%的早期卵巢癌; 2）发现周细胞作为抗血管生成治疗的靶; 3）观察到阿柏西普的反应率为39%（VEGF-Trap）和多西他赛对抗铂抗性疾病; 4）检测具有PTEN突变的卵巢癌中对AKT抑制剂哌立福新的应答; 5）发现多达30%的卵巢癌患者具有BRCA功能障碍;以及6）鉴定PVT-1和PFDN 4作为siRNA治疗的靶标。下一个资助期提出的五个项目将：1）评估用于卵巢癌早期检测的多标志物算法; 2）靶向Dll 4/Notch信号传导以逆转耐药性并与抗VEGF治疗协同作用; 3）用MEK、AKT和IGFR抑制测试低级别癌症的个性化治疗; 4）对具有活化PI 3 K信号传导或BRCA功能障碍的高级别卵巢癌的个性化治疗;和5）在临床前和临床研究中开发间充质干细胞作为IFN-B向肿瘤递送的载体。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;和病理学。将为DRP和CDP接受者提供支持，以获得同行审查的资金。内部、外部和倡导顾问将继续提供宝贵的建议。