Personalized preclinical models in pancreas cancer: a tractable approach to precision medicine

胰腺癌的个性化临床前模型：一种易于处理的精准医疗方法

• 批准号: 10372089
• 负责人: Richard Andrew Burkhart
• 金额: $ 26.27万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10372089
• 关键词: Advisory Committees; Aftercare; Award; Basic Science; Biological Markers; Biology; Biopsy; Cancer Biology; Cancer Center; Cancer Etiology; Caring; Cell Line; Cessation of life; Chemotherapy and/or radiation; Clinic; Clinical; Clinical Oncology; Clinical Research; Clinical Treatment; Clinical Trials; Clinical Trials Design; Colon Carcinoma; Combined Modality Therapy; Comprehensive Cancer Center; Culture Techniques; Cytotoxic Chemotherapy; Data; Development; Development Plans; Diagnosis; Disease; Disease model; Environment; Excision; Exposure to; Extramural Activities; Fostering; Foundations; Funding; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genetic; Genotype; Glean; Goals; Guidelines; Heterogeneity; Image; Immune; Immunotherapy; In Vitro; Individual; Institutes; Institution; K-Series Research Career Programs; Knowledge; Laboratories; Leadership; Life; Losartan; Malignant neoplasm of pancreas; Mentors; Mentorship; Methods; Microsatellite Instability; Modeling; Molecular; Newly Diagnosed; Nivolumab; Operating Rooms; Operative Surgical Procedures; Organoids; Outcome; Pancreatic Ductal Adenocarcinoma; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Pre-Clinical Model; Precision medicine trial; Precision therapeutics; Primary Neoplasm; Radiation; Radiation therapy; Randomized; Recommendation; Recording of previous events; Recurrence; Research; Research Personnel; Research Training; Resectable; Resected; Resources; Role; Safety; Science; Scientist; Speed; Surgeon; Surgical Oncology; Systemic Therapy; Testing; Therapeutic; Time; Translational Research; United States; Universities; Unresectable; Work; advanced disease; base; cancer care; career development; chemotherapy; clinically actionable; clinically relevant; design; drug sensitivity; experience; four-arm trial; hormone therapy; immunohistochemical markers; improved; malignant breast neoplasm; molecular marker; novel; novel therapeutics; operation; patient derived xenograft model; patient oriented; patient screening; personalized therapeutic; precision medicine; programs; recruit; response; tool; translational cancer research; treatment response; treatment strategy; tumor; tumor heterogeneity; two-dimensional

Project Summary/Abstract Built upon a history of sustained commitment to becoming a clinician scientist, the goal of this proposal is to become an independent investigator and leader in the field of translational cancer research and molecularly- guided precision medicine trials in pancreatic ductal adenocarcinoma (PDAC). PDAC impacts over 50,000 people annually in the United States and will soon become the second leading cause of cancer-related death. Two tractable strategies to increase survival in this devastating disease are: (1) to increase the utilization of potentially curative surgical resection, and (2) to identify the optimal systemic therapy for each patient amongst the cadre of agents currently prescribed in the clinic. To evaluate these strategies, this proposal is based upon a multi-center, randomized, phase II clinical trial investigating the safety and efficacy of an aggressive surgical approach to borderline resectable and locally advanced disease after combination cytotoxic chemotherapy, radiation, and immunotherapy. In the context of this trial, we will also evaluate the capacity of a novel culture technique, termed organoids, to provide clinically-actionable molecular data and guide precision medicine approaches. Taken together, this proposal evaluates a treatment strategy that may result in a curative operation for an additional 20-40% of newly diagnosed PDAC patients (10 - 20,000 US citizens annually) and will evaluate a tool for selection of best systemic therapy for each PDAC patient to provide a durable survival. To foster a transition to independence and enable leadership in future projects, translational research efforts will be supplemented during the award period with a formal career development plan. This plan is guided by the mentorship of Dr. Elizabeth Jaffee, a renowned leader in the field of translational research in PDAC and the deputy director of the Comprehensive Cancer Center at Johns Hopkins University (JHU). As an extramurally-funded researcher with an expertise in immune-focused and molecularly-guided clinical trials, Dr. Jaffee is an ideal mentor. An advisory committee has been established to include the world’s leading expert in PDAC organoids, Dr. David Tuveson, and a leader in surgical science initiatives, Dr. Christopher Wolfgang. I have joined the Division of Surgical Oncology as a surgeon-scientist with 75% protected research time. The research and training plan will be completed at JHU, one of the world’s leading institutions for pancreatic cancer care and a top-ranked research institution. In the rich environment and resources of JHU, I will pursue didactic coursework in the design and conduct of novel translational research and clinical trials. To reach independence as a surgeon-scientist, I will also draw upon the resources of a formal K-to-R transition program administered by the JHU Institute for Clinical and Translational Research. Support through the K08 Career Development Awards Program will be critical in helping me to achieve a long-term goal of serving as a leader in molecularly-guided precision medicine trials that have the potential to redefine outcomes in PDAC.

项目总结/文摘