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.

Public Health Relevance

to Public Health Lung cancer is the leading cause of cancer-related mortality among both men and women in the United States, leading to more deaths than the next three cancers combined. Among patients with metastatic disease, median survival is approximately 1 year, and less than 1% of patients are alive after 5 years. Rational targeted approaches offer the possibility of great improvements in outcomes for patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Lim, Susan E
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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Garon, Edward B; Christofk, Heather R; Hosmer, Wylie et al. (2014) Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer. J Cancer Res Clin Oncol 140:443-52
Krysan, Kostyantyn; Kusko, Rebecca; Grogan, Tristan et al. (2014) PGE2-driven expression of c-Myc and oncomiR-17-92 contributes to apoptosis resistance in NSCLC. Mol Cancer Res 12:765-74
Kris, Mark G; Johnson, Bruce E; Berry, Lynne D et al. (2014) Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311:1998-2006
Garon, Edward B; Finn, Richard S; Hamidi, Habib et al. (2013) The HSP90 inhibitor NVP-AUY922 potently inhibits non-small cell lung cancer growth. Mol Cancer Ther 12:890-900
Garon, Edward B; Pietras, Richard J; Finn, Richard S et al. (2013) Antiestrogen fulvestrant enhances the antiproliferative effects of epidermal growth factor receptor inhibitors in human non-small-cell lung cancer. J Thorac Oncol 8:270-8