Obesity and Pancreatic Cancer Progression and Survival

肥胖与胰腺癌的进展和生存

• 批准号: 10204947
• 负责人: Ana Babic
• 金额: $ 14.95万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-04 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204947
• 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

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.

项目总结/摘要 候选人的长期职业目标，最初作为分子生物学家接受培训，现在在 癌症流行病学研究，是成为一个独立的研究人员在分子流行病学的 胰腺癌胰腺癌是美国癌症死亡的第三大原因，并且被投射到 到2030年成为第二大原因。目前尚无基于人群的筛查， 选择有限，导致5年生存率仅为8%。识别导致 胰腺癌将为靶向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，与以下疾病的风险增加有关 胰腺癌和较短的患者生存期;然而，这些关联背后的机制是 不太了解。在她之前的工作基础上，她将瘦素信号确定为潜在的 肥胖和胰腺癌之间的介质，候选人试图填补这一知识空白，通过确定 肥胖和胰腺癌之间的其他分子通路和改变。的中心假设 这一观点认为肥胖改变了胰腺肿瘤细胞的致癌途径，促进了肿瘤生长， 进展该假设将使用几个大的患者人群进行测试， 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， 库存血浆样品和基因组学表征的胰腺肿瘤标本。具体而言是 候选人提出：1）表征将诊断前肥胖与较短的生存期联系起来的机制， 胰腺癌患者，2）评估肥胖相关脂肪因子信号传导和炎症在 癌症进展和患者存活率，以及3）鉴定富含肥胖相关的遗传标记， 胰腺癌这项对肥胖相关的系统性和多学科的全面评估， 基于肿瘤组织的改变将有助于确定胰腺癌进展的途径， 对疾病筛查和治疗具有重要意义。为了实现这些研究目标，作为 为了实现她的长期职业目标，候选人需要进一步接受流行病学培训， 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。 陈公共卫生学院，讲习班，研讨会，并参加国家会议。她将 由流行病学、生物统计学、分子生物学和生物学领域的专家组成的跨学科咨询小组指导。 病理学、癌症生物学和基因组学。因此，该奖项将为候选人提供知识 和专业知识，以实现她的近期研究目标，同时还提供职业指导， 候选人转变为胰腺癌分子流行病学的独立研究者。