Obesity and Pancreatic Cancer Progression and Survival

项目摘要/摘要 候选人的长期职业目标，最初是作为分子生物学家接受培训的，现在在 癌症流行病学研究，是成为分子流行病学的独立研究员 胰腺癌。胰腺癌是美国癌症死亡的第三大原因，预计 到2030年成为第二大事业。没有基于人群的筛查可用，而且具有治疗性 选择有限，导致5年存活率只有8%。确定导致疾病发生的分子机制 胰腺癌将为有针对性的疾病筛查和新的治疗策略创造机会。 肥胖是一种影响超过三分之一美国成年人口的疾病，它与患肥胖症的风险增加有关 胰腺癌和较短的患者生存期；然而，这些关联背后的机制是 人们对此知之甚少。在她之前的工作的基础上，她发现瘦素信号是潜在的 肥胖症和胰腺癌之间的中介，候选人试图通过确定 将肥胖和胰腺癌联系起来的其他分子途径和改变。的中心假说 这一建议是肥胖改变胰腺肿瘤细胞的致癌途径，促进肿瘤生长和 进步。这一假设将在几个大的患者群体中进行验证，这些患者具有广泛的 临床病理信息，基于计算机断层扫描(CT)成像的脂肪组织测量， 储存的血浆样本和具有基因组特征的胰腺肿瘤样本。具体地说， 候选人建议：1)描述诊断前肥胖与更短的生存期之间的联系机制 胰腺癌患者，2)评估肥胖相关脂肪因子信号转导和炎症在 癌症进展和患者存活率，以及3)识别与肥胖相关的丰富的基因特征 胰腺癌。这项全面和跨学科的肥胖相关系统性和跨学科评估 基于肿瘤组织的改变将有助于识别导致胰腺癌进展的途径， 对疾病筛查和治疗的重要意义。为了实现这些研究目标，如 为了实现她的长期职业目标，候选人需要接受进一步的流行病学培训， 生物统计学和肿瘤遗传学。这些知识将通过哈佛T.H.的课程学习获得。 陈氏公共卫生学院、讲习班、研讨会和参加全国会议。她会成为 由流行病学、生物统计学、分子生物学专家组成的跨学科咨询团队提供指导 病理学、癌症生物学和基因组学。因此，这一奖项将为候选人提供知识 和专业知识来实现她的近期研究目标，同时也提供职业指导，使 候选人转变为胰腺癌分子流行病学的独立研究员。

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.