Obesity and Pancreatic Cancer Progression and Survival

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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.