Novel systemic therapy to improve clinical outcome in small cell lung cancer

描述(由申请人提供)：这位候选人是埃默里大学血液学和内科肿瘤学的助理教授。他的长期职业目标是成为一名独立的翻译研究员，在肺癌患者的临床护理方面拥有公认的卓越专业知识，进行临床试验，从而开发新的 小细胞肺癌(SCLC)的治疗选择，以及可能发展为小细胞肺癌(SCLC)有效疗法的新化合物的临床前评估。候选人有兴趣通过研究新的治疗方案和开发有效的策略来提高现有治疗方法的疗效，从而提高小细胞肺癌患者的护理和临床结果。这位候选人提出了一项职业发展计划，其中包括一个多方面的培训和指导计划，旨在提供紧张的、以患者为导向的研究体验。这些目标将通过他在设计和实施两项招募小细胞肺癌患者的临床试验中的领导作用来实现。第一个试验是由候选人设计的一项单一机构研究，将评估三氧化二砷对复发疾病的临床疗效。如果成功，这项临床试验将为难治性患者群体的治疗选择引入一种新的疗法。第二个临床试验是候选人的 临床前实验室工作旨在评估添加口服PARP抑制剂ABT-888是否会在不增加毒性的情况下增强新诊断的小细胞肺癌患者的标准化疗药物的疗效。这项研究计划通过ECOG已建立的合作小组机制进行多机构临床试验。此外，为了准备长期从事翻译科学家的职业生涯，候选人提议在这段指导培训期间通过将肿瘤样本异种移植到免疫缺陷小鼠来建立小细胞肺癌肿瘤库。这一独特的资源将支持正在进行的和未来的新抗癌药物的临床前评估，并促进对小细胞肺癌独特生物学的了解。与这种以患者为中心的研究的紧张实践经验同时，候选人将参加一个正式的、结构良好的 授课课程使他获得了他的母校埃默里大学临床研究理学硕士学位。这门课程是一个严格的多年课程，旨在为参与者提供深入的知识和对以患者为中心的研究的伦理、设计、实施和监管的全面理解。这种全面的培训和实践经验将在Fadlo Khuri博士的领导下进行，Fadlo Khuri博士是一位成就卓著的翻译研究员，曾成功指导过所有临床医生和基础科学家干部。他将得到具有互补专业知识的共同导师的协助，这些导师包括在肺癌方面拥有精湛专业知识的国际知名临床研究员Suresh Ramalingam医学博士、经验丰富的基础科学家和mTOR生物学世界领先者孙世勇博士，以及对评估有前景的抗癌药物的临床试验设计有浓厚兴趣的生物统计学家Mourad Tighiouart博士。该培训计划将在埃默里大学和埃默里大学温希普癌症研究所举行，这两所大学为以患者为中心的研究提供了一个理想的学习、培训和实践环境，并为基础科学家和临床研究人员之间的合作提供了一个独特的机会。温希普癌症研究所是NCI指定的癌症中心，它确保由研究人员发起的单中心研究的适当进行以及参与大型合作小组 本申请中建议的临床试验。预计在此辅导期结束时，候选人将为从事以SCLC为重点的独立研究事业做好充分准备，并将在研究资金和学术领导角色方面具有极强的竞争力。

DESCRIPTION (provided by applicant): This candidate is an Assistant Professor in Hematology and Medical Oncology at Emory University. His long- term career goal is to become established as an independent translational researcher with recognized superior expertise in clinical care of lung cancer patients, conduct of clinical trials leading to the development of new treatment options for small cell lung cancer (SCLC) and in the preclinical evaluation of novel compounds likely to develop into effective therapy for SCLC. The candidate is interested in advancing the care and clinical outcome of SCLC patients by investigating new treatment options and developing effective strategies to improve on the efficacy of currently available therapies. The candidate has proposed a career development plan that includes a multi-faceted training and mentoring program designed to provide an intense, patient- oriented research experience. These goals will be achieved through his lead role in the design and conduct of two clinical trials enrolling SCLC patients. The first trial is a single institution study designed by he candidate that will evaluate the clinical efficacy of arsenic trioxide in relapsed disease. If successful, this clinical trial will introduce a novel therapy into the treatment options for the refractory patient population. The second clinical trial is a direct translation of the candidate's preclinical laboratory work designed to evaluate whether the addition of ABT-888, an orally administered PARP inhibitor, will enhance the efficacy of standard chemotherapy agents without increased toxicity in newly diagnosed SCLC patients. This study is planned as a multi-institution clinical trial to be conducted through the established cooperative group mechanism of ECOG. Additionally, in preparation for a long term career as a translational scientist, the candidate proposes the establishment of a SCLC tumor bank by xenogeneic transplantation of tumor samples to immunodeficient mice during this period of mentored training. This unique resource will support ongoing and future preclinical evaluation of new anticancer agents and facilitate the understanding of the unique biology of SCLC. Simultaneous with this intense practical experience in patient-oriented research, the candidate will participate in a formal well-structured didactic curriculum leading to the award of a Masters of Science in Clinical Research from his home institution, Emory University. This course of study is a rigorous multi-year curriculum designed to provide participants with a deep knowledge and comprehensive understanding of the ethics, design, conduct and regulation of patient-oriented research. This overall training and practical experience will occur under the lead mentorship of Dr. Fadlo Khuri, an accomplished translational researcher with track record of successfully mentoring all cadres of clinicians and basic scientists. He will be assisted by co-mentors with complementary expertise including Suresh Ramalingam, MD, an internationally renowned clinical investigator with superb expertise in lung cancer; Shi-Yong Sun, PhD, a highly experienced basic scientist and a world leader in mTOR biology; and Mourad Tighiouart, PhD, a biostatistician with strong interest in design of clinical trials to evaluate promising anticancer agents. This training program will occur at Emory University and the Winship Cancer Institute of Emory University which provide an ideal environment for learning, training and practical exposure in patient-oriented research and a unique opportunity for collaboration between basic scientists and clinical investigators. The Winship Cancer Institute is an NCI-designated cancer center which ensures the proper conduct of investigator-initiated single center studies as well as participation in large cooperative group clinical trials as proposed in this application. It is expected that at the end of this mentoring period, the candidate will be adequately prepared to pursue an independent research career focused on SCLC and will be highly competitive for research funding and academic leadership roles.