Inhibiting EGFR and ER pathways in NSCLC

抑制 NSCLC 中的 EGFR 和 ER 通路

• 批准号: 8505405
• 负责人: EDWARD B GARON
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8505405
• 关键词: Antiestrogen Therapy; Area; Aromatase; Award; Basic Science; Biological Assay; Biological Markers; Blood; Blood specimen; Breast; California; Cancer Etiology; Cancer Patient; Cessation of life; Chairperson; Chest; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Research Curriculum Award; Clinical Sciences; Clinical Trials; Cohort Studies; Combined Modality Therapy; Comprehensive Cancer Center; Conduct Clinical Trials; Data; Databases; Development Plans; Disease; Doctor of Medicine; Doctor of Philosophy; Educational process of instructing; Enrollment; Environment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptors; Estrogens; Etiology; European; Evaluation; Faculty; Fulvestrant; Funding; Gelatinase B; Goals; Grant; Growth; Growth Factor; Hematology; In Vitro; Incidence; Inpatients; Institutional Review Boards; International; Investigation; Jonsson Comprehensive Cancer Center of University of California Los Angeles; Journals; K-Series Research Career Programs; Laboratories; Lead; Learning; Letters; Los Angeles; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Manuscripts; Master of Science; Medical; Medical Oncology; Medicine; Mentors; Mentorship; Mutation; Non-Small-Cell Lung Carcinoma; Nurse Practitioners; Nursing Staff; Outcome; Pathway interactions; Patients; Peer Review; Phase; Phase II Clinical Trials; Physicians; Play; Positioning Attribute; Preparation; Progesterone; Progesterone Receptors; Progestins; Prognostic Marker; Progression-Free Survivals; Public Health; Randomized; Randomized Clinical Trials; Relative (related person); Replacement Therapy; Research; Research Personnel; Research Proposals; Research Training; Resistance; Resources; Risk; Role; Safety; Sampling; Scientist; Series; Signal Pathway; Signal Transduction; Site; Specimen; Staging; Structure; Subgroup; Telephone; Time; Tissue Sample; Tissues; Training; Training Programs; Translational Research; United States; United States National Institutes of Health; Universities; Woman; Work; Writing; anticancer research; arm; base; cancer research center director; carcinogenesis; career; career development; cigarette smoking; design; enzyme biosynthesis; improved; in vivo Model; inhibitor/antagonist; meetings; member; men; mortality; oncology; patient oriented; patient oriented research; pre-clinical; professor; prospective; research study; response; symposium; trial comparing; tumor

DESCRIPTION (provided by applicant): I, Edward B. Garon, M.D., am an Assistant Professor of Medicine in the Division of Hematology and Oncology at UCLA with a focus in lung cancer. My short term goals are to receive training in the conduct of clinical/translational research, to complete a clinical trial of erlotinib alone vs. erlotinib plus fulvestrant, and to evaluate clinical and correlative data generated as part of this trial. My career goals are: 1) Research- To develop investigator-initiated trials based on my laboratory work and develop into an independent scientist who can successfully compete for peer-reviewed funding. 2) Clinical- To become an academic leader in thoracic medical oncology, focused on patient-oriented research. In order to achieve these goals, I have designed a career development plan that includes extensive, highly structured mentorship and didactic training. The University of California, Los Angeles (UCLA) is one of the world's leading research and teaching universities, conducting a full spectrum of research in basic and clinical science. The UCLA Jonsson Comprehensive Cancer Center (JCCC) members include nearly 300 physicians and scientists. Clinical trials are conducted across a wide range of malignancies. The affiliated Translational Oncology Research International (TORI) Network encompasses 27 practices with 154 physicians in 67 offices. At least 80% of my overall time will be devoted to research related activities. I have been provided with personal office space, access to a call center for clinical calls, medical assistants, nursing staff, and a nurse practitioner (25%). My clinical responsibilities will be limited to 1 month of inpatient responsibility per year and one half-day of clinic per week. The institutional commitment to my project and my career are described in a letter from Dennis J. Slamon, M.D., Ph.D., chairman of the Division of Hematology/Oncology. Judith Gasson, JCCC director, has also written a letter describing resources that will be available to me through the JCCC. I will receive primary mentorship from Steven M. Dubinett, M.D. Dr. Dubinett been a successful mentor for trainees at all levels for more than 20 years. His successful track record of mentorship in lung cancer research includes numerous junior faculty who have been career development award recipients. The majority of these awardees have gone on to successful careers as independent investigators. These trainees are noted in Dr. Dubinett's trainee list in this application. Dr. Dubinett has lead the UCLA Lung SPORE training program for the past ten years and is also the PI for two NIH T32 training grants. He served on the training committee for the TRWG. I will meet weekly with Dr. Dubinett during the award period. Topics covered in our meetings will include review of data and planning of experiments; manuscript and proposal preparation and career advice. I will also meet monthly with my Mentorship Committee consisting of Dennis J. Slamon, M.D., Ph.D., Robert Elashoff, Ph.D., and Richard J. Pietras M.D., Ph.D. Dr. Dubinett will also attend these meetings. In addition, I will have monthly phone calls and thrice yearly meetings with my external advisor, Jill Siegfried, Ph.D. I will be in a highly structured, protected and stimulating research environment devoted to translational research in lung cancer. I have enrolled in the UCLA K30 Graduate Training Program in Translational Investigation to receive a Master of Science Degree in Clinical Research. Timing of the coursework has been tailored in order to optimally benefit my proposed research plan. Additional focus during the training program will be directed to manuscript and grant writing. In addition, I will attend departmental and divisional research conferences, weekly laboratory meetings, clinical research meetings, and journal clubs. I will continue to attend the JCCC seminar series which includes a monthly seminar focused on lung cancer. My research proposal entails evaluation of the role of the estrogen receptor (ER) pathway in combination with the epidermal growth factor receptor (EGFR) pathway in non-small cell lung cancer (NSCLC). 1) I will complete a clinical trial of erlotinib alone or in combination with fulvestrant. 102 Patients with Stage IIIB or IV NSCLC and at least one prior line of therapy (unless patient refuses other therapy) will be enrolled on this phase II, randomized clinical trial conducted at UCLA and through the TORI Network. The project received approval from the UCLA IRB, WIRB (for TORI sites), UCLA ISPRC, and it received IND approval from the FDA. 51 of the projected 102 patients have been enrolled. The primary objective of the study is to determine the response rate in each arm. Secondary objectives include progression-free survival, overall survival and safety. 2) I will evaluate blood samples collected as part of the clinical trial for biologic markers, including estradiol and investigational biomarkers NGAL and MMP-9, and 3) I will evaluate tissue collected as part of the clinical trial for correlative secondary endpoints, including tumor levels of ER, ER, progesterone receptor, aromatase and EGFR as well as EGFR mutations and other selected biologic markers. At the conclusion of this project, I will be able to conduct investigator-initiated clinical trials with extensive correlative analysis. This will be accomplished by conducting the proposed research, receiving mentorship during the course of this project, and didactic learning through the UCLA Masters of Science in Clinical Research (K30) Program. At the conclusion of this research training, I will be well positioned to function as an independent physician scientist in patient-oriented lung cancer research, and I anticipate competing for independent research funding.

简介（由申请人提供）：我，Edward B. Garon，医学博士，是加州大学洛杉矶分校血液学和肿瘤学部门的医学助理教授，专注于肺癌。我的短期目标是接受临床/转化研究方面的培训，完成一项单独厄洛替尼与厄洛替尼加氟维司汀的临床试验，并评估该试验产生的临床和相关数据。我的职业目标是：1)研究——在我的实验室工作的基础上开展研究者发起的试验，并发展成为一名独立的科学家，能够成功地竞争同行评审的资金。2)临床-成为胸内科肿瘤学的学术领导者，专注于以患者为导向的研究。为了实现这些目标，我设计了一个职业发展计划，包括广泛的、高度结构化的指导和教学培训。加州大学洛杉矶分校（UCLA）是世界领先的研究和教学大学之一，在基础科学和临床科学领域开展全方位的研究。加州大学洛杉矶分校约翰逊综合癌症中心（JCCC）的成员包括近300名医生和科学家。临床试验是针对各种恶性肿瘤进行的。附属的国际转化肿瘤学研究（TORI）网络包括67个办公室的154名医生的27个实践。