HCC Ovarian Cancer SPORE

HCC 卵巢癌孢子

基本信息

批准号：
10713050
负责人：
Ronald J Buckanovich
金额：
$ 216.38万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10713050
关键词：
Address Advocate American Archives BRCA1 gene Bioinformatics Biometry Bromodomains and extra-terminal domain inhibitor Cancer Center Cancer Etiology Cancer Patient Carboplatin Cell Cycle Checkpoint Cell Cycle Checkpoint Genes Cells Cessation of life Chemoresistance Clinical Clinical Data Clinical Trials Collaborations Cost Sharing DNA Repair Development Diagnosis Disease Disease Progression Disease Resistance Doctor of Philosophy Dose EZH2 gene Ensure Epigenetic Process Erinaceidae Exclusion Experimental Models Funding Future Generations Goals Human Immune Immune checkpoint inhibitor Immunotherapy In Vitro Incidence Individual Institution Investments Malignant Neoplasms Malignant neoplasm of ovary Mediating Mesenchymal Stem Cells Minority Groups Mitotic Modeling Molecular Myeloid-derived suppressor cells New Agents Newly Diagnosed Operative Surgical Procedures Pathology Patient Care Patient-Focused Outcomes Patients Pennsylvania Phase Phase Ib Trial Platinum Poly(ADP-ribose) Polymerase Inhibitor Positioning Attribute Prediction of Response to Therapy Principal Investigator Prognosis Program Research Project Grants Proteins Recurrence Relapse Research Research Infrastructure Research Personnel Resistance Resource Sharing Science Scientist Signal Transduction TOPBP1 Gene Technology Testing Time Translational Research Underrepresented Minority Woman anticancer research cancer care career career development checkpoint therapy chemotherapy data resource design experience homologous recombination improved improved outcome in vivo inhibitor inhibitor therapy innovation mortality multidisciplinary multipotent stromal progenitor notch protein novel diagnostics novel therapeutic intervention novel therapeutics patient response personalized medicine phase II trial potential biomarker pre-clinical prevent programs recruit response smoothened signaling pathway stem cells stromal progenitor success synergism therapeutic development therapy resistant tissue resource treatment strategy tumor tumor microenvironment

项目摘要

PROJECT SUMMARY/ABSTRACT – OVERALL Ovarian cancer (OvCa) has the third highest mortality to incidence ratio and is the fifth leading cause of cancer death in American women. The typical disease course of a patient with OvCa spans four and a half years from the time of diagnosis to death. During the course of patient care, acquired and innate resistance to our most effective and promising therapies, such as chemotherapy, PARP inhibitor therapy, and immunotherapy, drives disease progression. The overall goal of the UPMC Hillman Cancer Center (HCC) OvCa SPORE is to prevent and/or overcome therapeutic resistance to improve patient survival. Each of the SPORE’s three Projects evolved from the innovative concepts and findings of SPORE investigators. Each project involves a clinical trial with a new agent. In addition, each project, through complementary investigator expertise, incorporates critical translational aims to identify patients most likely to respond to therapy. Project 1 will assess the ability of inhibitors of the epigenetic regulator EZH2 to prevent/overcome OvCa stromal progenitor cell-driven resistance to platinum-based chemotherapy. Project 2 will determine whether BET inhibitors, which downregulate critical DNA repair and cell cycle checkpoint proteins, can reverse resistance to PARP inhibitors. Project 3 will test whether inhibitors of the hedgehog signaling pathway, which drives tumor immune exclusion, can improve OvCa patient response to immune checkpoint inhibitor therapy. The HCC OvCa SPORE will include a Career Enhancement Program (CEP) and Developmental Research Program (DRP) in order to both encourage early career investigators to enter the field of translational OvCa research and engage more established investigators in OvCa research. The CEP and the DRP, which are cost-shared and proactive at providing research funding to investigators from under-represented minority groups, will provide a pipeline of potential future SPORE Projects. All SPORE, CEP, and DRP Projects will be receive fiscal and scientific oversight from an Administrative Core and support from two shared resource cores. The Translational Pathology Core will collect, annotate, archive, and distribute biospecimens and clinical data derived from the more than 300 HCC OvCa patients seen each year. It will also develop new preclinical experimental models that behave more like human OvCa. The Biostatistics and Bioinformatics Core will aid in design and analysis of all studies, including ‘omic’ technologies that can provide molecular and spatial characterization of individual cells within a tumor. The SPORE Projects will also be supported by established and new collaborators who are internal and external to HCC. Combined, the SPORE projects, CEP, DRP, and cores are positioned, together with our vertical collaborators, to improve the outcomes of patients with ovarian cancer. The findings generated by the SPORE will be advanced through further collaboration and future non-SPORE funding.

项目摘要/摘要 - 总体 Ovarian cancer (OvCa) has the third highest mortality to incidence ratio and is the fifth leading cause of cancer death in American women. The typical disease course of a patient with OvCa spans four and a half years from The time of diagnosis to death. During the course of patient care, acquired and innate resistance to our most Effective and promise therapies, such as chemotherapy, PARP inhibitor therapy, and immunotherapy, drives 疾病进展。 The overall goal of the UPMC Hillman Cancer Center (HCC) OvCa SPORE is to prevent and/or overcome therapeutic resistance to improve patient survival. Each of the SPORE’s three Projects Evolved from the innovative concepts and findings of SPORE investigators. Each project involves a clinical trial with a new agent. In addition, each project, through complementary investigator expertise, incorporates critical Translational aims to identify patients most likely to respond to therapy. Project 1 will assess the ability of inhibitors of the epigenetic regulator EZH2 to prevent/overcome OvCa stromal progenitor cell-driven resistance to platinum-based chemotherapy. Project 2 will determine whether BET inhibitors, which downregulate critical DNA repair and cell cycle checkpoint proteins, can reverse resistance to PARP inhibitors. Project 3 will test Whether inhibitors of the hedgehog signaling pathway, which drives tumor immune exclusion, can improve OvCa patient response to immunocheckpoint inhibitor therapy. The HCC OvCa SPORE will include a Career Enhancement Program (CEP) and Developmental Research Program (DRP) in order to both encourage early career investigators to enter the field of translational OvCa research and engage more established investigators in OvCa research. The CEP and the DRP, which are cost-shared and proactive at providing research funding to investigators from under-represented minority groups, will provide a pipeline of potential Future SPORE Projects. All SPORE, CEP, and DRP Projects will be received fiscal and scientific oversight from an Administrative Core and support from two shared resource cores. The Translational Pathology Core will collect, annotate, archive, and distribute biospecimens and clinical data derived from the more than 300 HCC OvCa patients see each year. It will also develop new preclinical experimental models that behave more like human OvCa. The Biostatistics and Bioinformatics Core will aid in design and analysis of all studies, including 'omic' technologies that can provide molecular and spatial characterization of individual cells within a tumor. The SPORE Projects will also be supported by established and new collaborators who are internal and external to HCC. Combined, the SPORE projects, CEP, DRP, and cores are positioned, together with our vertical collaborators, to improve the outcomes of patients with ovarian cancer. The findings generated by the SPORE will be advanced through further collaboration and future non-SPORE funding.