Training in Cancer Therapeutics Research

 描述(由申请人提供)：在过去的25-30年里，我们对人类癌症发展的分子遗传学和生物学的基本理解取得了巨大的进步。这种对癌症关键特征的认识的增强，导致了治疗个别癌症的新型药物和治疗方案的加速开发，现在每年都有越来越多的新药获得美国食品和药物管理局的批准。然而，尽管取得了这些重大进展，但无论是细胞毒化疗、靶向治疗和/或免疫治疗，这些新疗法的最终临床疗效仍然面临着巨大的挑战。一般来说，一旦诊断出晚期疾病，患者就无法治愈。因此，仍然迫切需要培训具有癌症治疗专业知识的个人。尤其重要的是，培训对基础科学概念有扎实理解的个人，使他们能够更有效和成功地将基本实验室发现转化为临床环境，并将相关科学纳入临床试验，从而为基础科学提供信息。不幸的是，基础科学家和翻译/临床研究人员之间的互动水平仍然不足，这在很大程度上是因为这两个世界在他们的范围和优先事项上是如此不同。因此，我们相信，对临床前和临床/转化学领域的内科科学家的培训将极大地推动癌症治疗领域的发展，最终目标是开发能够真正改变癌症患者生活的新型药物和治疗方案。人类癌症的成功治疗需要多学科和跨学科的综合方法。匹兹堡大学癌症研究所(UPCI)和血液肿瘤科致力于开发涵盖所有经典细胞毒性化疗药物、靶向治疗、免疫学药物和生物药物的新型癌症疗法。这一培训计划汇集了来自血液肿瘤科和匹兹堡大学医学院其他六个系的一批杰出的研究人员，培训机构的科学专长包括临床前、转化性和临床癌症治疗研究的整个连续体。这群科学家深知培养内科科学家的重要性，并建议通过实现以下目标来实现这一目标：(1)招募有前途的医学肿瘤学研究员，他们致力于与癌症治疗相关的学术医学肿瘤学；(2)提供专门的研究生水平的课程工作，以增强他们在分子和细胞生物学、免疫学、生物化学、药理学、遗传学和临床/转化医学方面的知识(3)通过与专注于癌症治疗的知名导师合作，深入接触基本研究技能。这项建议是为医学肿瘤学研究员提供一个培训计划，涵盖癌症治疗研究的整个范围，并包括基础科学、翻译科学和临床科学。该计划每一年将支持三名肿瘤学研究员。该培训计划将集中在5个明确的研究领域：(1)细胞毒性化疗；(2)靶向分子治疗；(3)免疫治疗；(4)化疗敏感性和耐药性的研究机制；以及(5)临床研究。每个研究领域都由我们的培训教员很好地代表，每个研究领域的代表都是执行委员会的成员。培训经验将包括正式的课程工作、研讨会、期刊俱乐部、基础实验室研究和临床/翻译研究。基础实验室和翻译研究将构成培训经验的主体。每个学员每年都将参加有关癌症药物开发、癌症生物学、信号传递、免疫学、生物化学、细胞生物学、遗传学和临床试验的原理和技术的研究生水平课程，以及每年负责任地进行研究的课程，这将为他们发展专注于癌症治疗的学术生涯提供必要的基础。受训者将进入导师实验室，为期两年，如果得到执行委员会的批准，还可以选择第三年的培训。评估和评价将每4个月进行一次，该评价将提交执行委员会。委员会会议结束后，受训者将与项目总监会面，届时受训者将被要求评估他/她在导师实验室的经历。在研究奖学金结束时，每个受训者需要一份两页的书面总结，评估他们的总体培训经验。我们预计，来自教师和实习生的反馈将分别提高该项目的整体学术生产率。

 DESCRIPTION (provided by applicant): Over the past 25-30 years, tremendous advances have been made in our fundamental understanding of the molecular genetics and biology that underlie the development of human cancer. This enhanced understanding of the critical hallmarks of cancer has led to an accelerated development of novel agents and treatment regimens to treat individual cancers, and an increasing number of new drugs are now being approved by the US Food and Drug Administration each year. However, despite these significant advances, there remain significant challenges to the ultimate clinical efficacy of thes new therapies whether they be cytotoxic chemotherapy, targeted therapy, and/or immunotherapy. In general, once advanced disease is diagnosed, the patient is incurable. As a result, there remains an urgent and critical need to train individuals with specific expertise in cancer therapeutics. It is especially important to train individuals with a solid understanding of basic science concepts who can then more effectively and successfully translate basic laboratory findings to the clinical setting as well as incorporate correlative science in clinical trials, which can subsequently inform the basic science. Unfortunately, there remains an insufficient level of interaction between basic scientists and translational/clinical investigators in large part because the two worlds are so different in their scope and priority. As such, we believe that the training of physician-scientists in both pre-clinical and clinical/translational science will greatly advance the field of cancer therapeutics with the eventual goal of developing novel agents and treatment regimens that can make a real difference in the lives of cancer patients. The successful treatment of human cancer requires an integrated multi- and inter-disciplinary approach. The University of Pittsburgh Cancer Institute (UPCI) and the Division of Hematology-Oncology are deeply committed to developing novel cancer therapeutics that span the entire range of classic cytotoxic chemotherapy agents, targeted therapies, immunologic agents, and biologic agents. This Training Program has brought together an outstanding group of investigators from the Division of Hematology-Oncology and from six other departments of the University of Pittsburgh School of Medicine, and the scientific expertise of the training faculy includes the entire continuum of pre-clinical, translational, and clinical cancer therapeutics research. This group of scientists understands the significance of training physician-scientists and proposes to achieve this goal by accomplishing the following aims: (1) Recruit highly promising medical oncology fellows, who are committed to a career in academic medical oncology relevant to the field of cancer therapeutics (2) Provide specific graduate-level course work to enhance their knowledge in molecular and cell biology, immunology, biochemistry, pharmacology, genetics, and clinical/translational medicine (3) Provide an in-depth exposure to basic research skills by working with well-established mentors who are focused on cancer therapeutics. This proposal is for a Training Program for medical oncology fellows that encompasses the entire range of cancer therapeutics research and includes basic, translational, and clinical science. Three medical oncology fellows will be supported for each year of the Program. This Training Program will focus on 5 defined research areas: (1) Cytotoxic Chemotherapy; (2) Targeted Molecular Therapy; (3) Immunotherapy; (4) Investigating Mechanisms of Chemosensitivity and Resistance; and (5) Clinical Investigations. Each of these research areas is well-represented by the members of our training faculty, and a representative of each research area is on the Executive Committee. The training experience will consist of formal course work, seminars, journal clubs, basic laboratory research, and clinical/translational research. Basic laboratory and translational research will form the bulk of the training experience. Each of the trainees will participate in graduate-level courses on the principles and techniques of cancer drug development, cancer biology, signaling, immunology, biochemistry, cell biology, genetics, and clinical trials, as well as courses on the responsible conduct of research each year, which will provide them with the necessary foundation to develop an academic career focused on cancer therapeutics. The trainees will enter a mentor's laboratory for two years, with an optional third year of training if approved by the Executive Committee. Assessment and evaluation will take place every 4 months and this evaluation will be presented to the Executive Committee. Following the Committee meeting, the trainee meets with the Program Director, at which time, the trainee will be asked to evaluate his/her experience in the mentor's laboratory. A two-page written summary by each trainee evaluating their overall training experience is required at the conclusion of the research fellowship. We anticipate that this feedback from faculty and trainees, respectively, will enhance the overall academic productivity of the program.