Insulin resistance in the development and progression of invasive bladder cancer

浸润性膀胱癌发生和进展中的胰岛素抵抗

• 批准号: 9284276
• 负责人: Ronac Mamtani
• 金额: $ 17.44万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-06 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9284276
• 关键词: Accounting; Address; Award; Benefits and Risks; Biological Markers; Biometry; Bladder; Bladder Neoplasm; Blood specimen; Case-Control Studies; Clinical; Clinical Data; Collaborations; Curative Surgery; Cystectomy; Data; Data Quality; Data Set; Databases; Development; Development Plans; Diabetes Mellitus; Diagnosis; Disease; Endocrinology; Enrollment; Epidemiology; Functional disorder; Future; Goals; Growth; Health; Incidence; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Integration Host Factors; Intervention; Intervention Studies; K-Series Research Career Programs; Knowledge; Lead; Link; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Medical; Medicine; Mentors; Mentorship; Metabolic; Metabolism; Methods; Modeling; Modernization; Modification; Morbidity - disease rate; Muscle; Neoplasms; Obesity; Observational Study; Operative Surgical Procedures; Outcome; Pathological Staging; Patient Care; Patient Selection; Patients; Pennsylvania; Performance; Play; Population; Positioning Attribute; Prevalence; Prior Chemotherapy; Prospective cohort; Prospective cohort study; Radical Cystectomy; Recurrence; Research; Research Methodology; Research Personnel; Risk; Risk Assessment; Risk Factors; Role; Selection for Treatments; Senior Scientist; Specimen; Staging; Structure; System; Testing; Time; Training; Translational Research; Tumor Pathology; Universities; Urogenital Cancer; aggressive therapy; base; biobank; biomarker discovery; cancer care; cancer recurrence; cancer therapy; career; career development; chemotherapy; clinical epidemiology; clinical practice; cohort; design; economic cost; experience; experimental study; improved; improved outcome; insight; interest; mortality; novel; oncology; patient oriented; patient oriented research; personalized approach; population based; professor; prognostic; prospective; public health relevance; response; risk selection; skills; success; theories; tool; tumor; tumor progression

 DESCRIPTION (provided by applicant): This application proposes a career development award for an Assistant Professor of Medicine in Oncology at the University of Pennsylvania with scientific interest in understanding the role of host factors, and their modification, on genitourinary cancer outcomes. During the course of this award, he will identify metabolic predictors of poor outcome in patients with muscle-invasive bladder cancer. This award will enable him to evolve into an independent investigator, conducting both population-based and patient-oriented research to inform a more personalized approach to genitourinary cancer therapy. New skills and further knowledge will be obtained in a 5-year career development plan that spans the fields of epidemiology, oncology, and endocrinology through (1) advanced training in epidemiology and biostatistics; (2) new training in translational research methodology; (3) new hands-on experience in prospective observational research; (4) intensive mentorship and collaboration with senior scientists; and (5) the performance of original research. To achieve these goals, the candidate has assembled a mentoring team with expertise in clinical epidemiology, bladder cancer care, metabolism, translational science, and biostatistics, all of whom are not only accomplished researchers but also successful mentors and leaders in their respective fields. Muscle-invasive tumor is the major cause of morbidity and mortality from bladder cancer. Pre-operative chemotherapy is associated with improved survival, but responses are seen in only 30-40% of patients. Current methods for predicting bladder cancer recurrence rely on tumor pathology, which is available only after surgery (cystectomy) and therefore cannot inform decisions about use of chemotherapy prior to cystectomy. Host-related factors associated with tumor recurrence have not yet been identified, although insulin resistance may play a role. This research will first employ a novel database to conduct a case-control study assessing clinical insulin resistance, defined as a diagnosis with diabetes and/or obesity, as a risk factor for the development of bladder cancer recurrence after cystectomy (AIM 1). Next, the candidate will conduct a prospective cohort study in patients treated with cystectomy to examine risk of bladder cancer recurrence in relation to subclinical insulin resistance (AIM 2), measured by homeostatic model assessment (HOMA). Results from these studies could be implemented into clinical practice to improve individualized prognostication and selection of patients likely to benefit from risk-reducing pre-operative chemotherapy. Finally, the candidate will create a biobank of bladder tumor specimens and blood samples from enrolled cohort patients which will be available for later biomarker discovery studies related to the applicant's current and future hypotheses. This training will enable the candidate to transition seamlessly between population- and patient-oriented methods, selecting the design best suited to answer each question. A structured training plan with rigorously mentored scientific study is proposed to position the candidate for independence at the end of five years.