U.T. M. D. Anderson Cancer Center SPORE in Ovarian Cancer

UT

• 批准号: 10005257
• 负责人: ROBERT C BAST
• 金额: $ 172.29万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-22 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005257
• 关键词: Achievement; Autoantibodies; Automobile Driving; BRCA1 Mutation; BRCA1 gene; BRCA2 gene; Biological Markers; Biology; Biopsy; Blood Vessels; CA-125 Antigen; CSF1R gene; Cancer Cell Growth; Cancer Center; Cancer Patient; Carboplatin; Caring; Cell Line; Cell Survival; Cell division; Centrosome; Chromatin; Clinic; Clinical; Clinical Data; Clinical Trials; Combined Modality Therapy; DNA; DNA Repair; DNA Repair Disorder; DUSP6 protein; Data; Defect; Development; Diagnosis; Disease; Doctor of Medicine; Drug Targeting; Drug resistance; Early Diagnosis; Enzymes; Evaluation; Faculty; Failure; Funding; Generations; Genes; Germ-Line Mutation; Goals; Grant; Growth; HDAC5 gene; Individual; Infrastructure; Interferons; International; Laboratories; MEKs; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mediating; Mesenchymal Stem Cells; Mitosis; Molecular; Monitor; Moon; Mutation; Ovarian; PIK3CA gene; PTEN gene; Paclitaxel; Paper; Pathway interactions; Patient-Focused Outcomes; Patients; Peer Review; Pharmaceutical Preparations; Phase; Phase Ia/Ib Trial; Philanthropic Fund; Phosphorylation; Phosphorylation Inhibition; Phosphotransferases; Platinum; Polyploidy; Predictive Value; Production; RNA; Recurrence; Research Personnel; Research Project Grants; Resistance; Retinoblastoma Protein; SERPINE1 gene; Serous; Services; Somatic Mutation; TP53 gene; Testing; Time; Translations; Tumor-associated macrophages; University of Texas M D Anderson Cancer Center; Wages; Woman; Xenograft procedure; angiogenesis; anticancer research; base; bevacizumab; biomarker identification; biomarker panel; cancer cell; cancer initiation; career; chemotherapy; design; docetaxel; homologous recombination; improved; improved outcome; inhibitor/antagonist; interest; knock-down; macrophage; malignant breast neoplasm; member; nanoassay; notch protein; novel; objective response rate; overexpression; peritoneal cancer; phase III trial; pre-clinical; preclinical study; predicting response; predictive marker; programs; protein biomarkers; recruit; resistance mechanism; response; response biomarker; screening; targeted agent; targeted treatment; tumor

Overall SUMMARY/ABSTRACT The overall goal of the University of Texas MD Anderson Cancer Center (MDACC) Ovarian Cancer SPORE is to improve outcomes for ovarian cancer patients by combining targeted agents based upon the molecular, cellular and clinical biology of their disease and understanding and targeting mechanisms of drug resistance. Over the last 6 years (FY2009-FY2015), MDACC has cared for 4,483 patients with ovarian, fallopian tube and peritoneal cancers. MDACC has given high priority to ovarian cancer research through recruitment, salary support, clinical facilities, laboratory space, and philanthropic funds. Over the last 6 years, MDACC has recruited six outstanding faculty members with an interest in ovarian cancer research (Drs. Amir Jazaeri, Larissa Meyer, Alpa Nick, Shannon Westin, Melinda Yates, and Behrouz Zand). Philanthropic support of the Women’s Cancer Breast-Ovarian Moon Shot has provided organization and infrastructure. Over the same time period, our previous SPORE funded 15 Developmental Research Projects (DRPs), and supported six Career Enhancement Program (CEP) awardees, and SPORE investigators have contributed 461 peer-reviewed papers pertaining to ovarian cancer with 53% (246) IF >5 and 20% (92) >10. Achievements included: 1) evaluation of a two stage screening strategy with a positive predictive value of >30% for detecting stage I-II disease in 9 of 12 cases detected; 2) identification of biomarkers that detect 18% of CA125 negative cases; 3) development of a point-of-service nanoassay for these biomarkers; 4) discovery that anti-TP53 autoantibodies rise 5 (median) -13 months (mean) prior to CA125, the first biomarker to provide earlier detection than CA125; 4) observation of a 54% objective response rate to anti-angiogenic therapy with aflibercept and docetaxel; 5) initiation of a trial targeting Dll4 and notch; 6 ) CSF1R inhibitors could deplete macrophages and reduce resistance to anti-VEGF Therapy 7) demonstration of significant activity of the MEK inhibitor selumetinib in low-grade ovarian cancers and initiation of an international phase III trial of another potent MEK inhibitor trametinib; 8) development of a robust biomarker panel that predicts response to PARP inhibitors (PARPi) and initiation of multiple trials combining PI3K and PARP inhibitors in high-grade ovarian cancer; and 9) use of mesenchymal stem cells to deliver interferon to ovarian cancers. I n t h i s new SPORE application, 4 projects will strive to: 1) validate predictive biomarkers and implement rational combination therapy with PARP inhibitors designed to overcome pre- existing and adaptive resistance; 2) validate predictive biomarkers and implement rational combination therapy with MEK inhibitor for low-grade ovarian serous cancers to overcome resistance; 3) target macrophages to overcome resistance to anti-VEGF therapies; and 4) evaluate a novel SIK2 inhibitor in a Phase IA/B trial and identify agents that produce synthetic lethality.

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