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.
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