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Obesity and Pancreatic Cancer Progression and Survival

肥胖与胰腺癌的进展和生存

基本信息

批准号：
10443747
负责人：
Ana Babic
金额：
$ 14.99万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-04 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10443747
关键词：
Address Adipose tissue Adult Advisory Committees Affect Award Basic Science Bioinformatics Biometry C-reactive protein CDKN2A gene Cancer Biology Cancer Etiology Cancer Patient Cessation of life Clinical Oncology Clinical Pathology DNA Repair Deposition Development Disease Education Educational workshop Endocrine Glands Environment Epidemiology Evaluation Fatty acid glycerol esters Fostering Frequencies Future Genes Genetic Genomics Goals Hormones Image Incidence Inflammation Interleukin-6 KRAS2 gene Knowledge Leptin Link MADH4 gene Malignant Neoplasms Malignant neoplasm of pancreas Measurement Measures Mediator of activation protein Mentors Mentorship Metabolism Methodology Molecular Molecular Epidemiology Molecular Genetics Mutation Non obese Obesity Obesity associated cancer Oncogenic Outcome PF4 Gene Pancreatic Ductal Adenocarcinoma Pathogenesis Pathway interactions Patient-Focused Outcomes Patients Plasma Population Prevalence Public Health Schools Research Research Personnel Resources Risk Role Sampling Signal Transduction Somatic Mutation Specimen Stage at Diagnosis Survival Rate TNF gene TNFRSF1A gene TP53 gene Testing Therapeutic Tissue Banks Training Transforming Growth Factor beta Tumor Tissue Tumor stage Visceral Vocational Guidance Work X-Ray Computed Tomography adipokines adiponectin angiogenesis base cancer epidemiology cancer genomics cancer survival career career development chromatin remodeling data archive energy balance epidemiology study genetic signature high body mass index imaging study improved inflammatory marker leptin receptor meetings molecular pathology novel therapeutic intervention obese person pancreatic cancer cells pancreatic cancer patients pancreatic neoplasm patient population population based receptor screening subcutaneous systemic inflammatory response tumor tumor growth tumor progression

项目摘要

PROJECT SUMMARY / ABSTRACT The long-term career goal of the candidate, originally trained as a molecular biologist and now working in cancer epidemiology research, is to become an independent investigator in molecular epidemiology of pancreatic cancer. Pancreatic cancer is the third-leading cause of cancer death in the U.S., and is projected to become the second leading cause by 2030. No population-based screening is available, and therapeutic options are limited, resulting in a 5-year survival rate of only 8%. Identifying molecular mechanisms leading to pancreatic cancer will create opportunities for targeted disease screening and new therapeutic strategies. Obesity, a condition affecting more than 1/3 of the adult U.S. population, is associated with increased risk of pancreatic cancer and with shorter patient survival; however the mechanisms behind these associations are poorly understood. Building on her prior work, where she identified leptin signaling as one of the potential mediators between obesity and pancreatic cancer, the candidate seeks to fill this knowledge gap by identifying additional molecular pathways and alterations linking obesity and pancreatic cancer. The central hypothesis of this proposal is that obesity alters oncogenic pathways in pancreatic tumor cells, promoting tumor growth and progression. This hypothesis will be tested using several large patient populations with extensive clinicopathological information, computed tomography (CT) imaging-based measurements of adipose tissues, banked plasma samples, and genomically characterized pancreatic tumor specimens. Specifically, the candidate proposes to: 1) characterize mechanisms linking prediagnostic obesity with shorter survival of pancreatic cancer patients, 2) evaluate the role of obesity-associated adipokine signaling and inflammation in cancer progression and patient survival, and 3) identify genetic signatures enriched in obesity-associated pancreatic cancers. This comprehensive and interdisciplinary evaluation of obesity-associated systemic and tumor tissue-based alterations will help identify pathways responsible for pancreatic cancer progression, with important implications for disease screening and treatment. In order to accomplish those research aims, as well as to attain her long-term career objective, the candidate requires further training in epidemiology, biostatistics, and tumor genetics. This knowledge will be obtained through coursework at the Harvard T.H. Chan School of Public Health, workshops, seminars, and participations in national meetings. She will be mentored by an interdisciplinary advisory team composed of experts in epidemiology, biostatistics, molecular pathology, cancer biology and genomics. This award will therefore provide the candidate with the knowledge and expertise to accomplish her near-term research goals, while also providing career guidance that will allow the candidate’s transition to an independent investigator in molecular epidemiology of pancreatic cancer.

项目摘要/摘要