Jennifer R. Diamond, MD is a clinician-scientist with strong training in translational breast cancer research with a strong commitment to developing new therapies for the treatment of triple-negative breast cancer. Dr. Diamond is an Assistant Professor of Medicine in the Division of Medical Oncology at the University of Colorado Denver (CU), where she serves as a bridge between the Breast Oncology and Developmental Therapeutics programs. Her long-term career goal is to lead a multidisciplinary research team in translating preclinical biomarker discovery into more effective """"""""personalized"""""""" medicine for patients with breast cancer. The candidate will develop expertise in translational clinical trial design and implementation, successful acquisition and interpretation of correlative tissue studies, and advanced topics in bioinformatics through this K23 Mentored Patient-Oriented Career Development Award. The candidate's short-term career goal is to establish herself as an independent investigator in developmental therapeutics and breast oncology with the preliminary data, research training, and publication record necessary to be competitive for NIH project grant funding. The K23 Mentored Patient-Oriented Research Career Development Award with help her to achieve these goals by: 1) granting her protected time to develop a clinical and translational research career under the guidance of a team of mentors dedicated to her success, 2) allowing her to receive specialized training in the design of biomarker-driven clinical trials, bioinformatics, and the responsible conduct of research through direct interaction with mentoring scientists and supplemental didactics, and 3) providing her the opportunity to gain recognition as a researcher in the field of drug development and breast oncology. The candidate's research plan aims to complete a single-arm, dual institution, two-stage phase II clinical trial of ENMD-2076 in patients with advanced or metastatic, previously treated TNBC that was conceived and designed by Dr. Diamond. This clinical trial is open to accrual as of July 2012 and funded by the NIH (1R21CA164617-01A1, PI Diamond). A secondary aim of this study is to explore genomic biomarkers predictive of clinical response to ENMD-2076 in this patient population based on unique preclinical data generated in Dr. Diamond's laboratory investigating p53-based genomic classifiers. The overall goal of this proposal is to develop novel and effective therapy for advanced TNBC, including the investigation of unique biomarker selection strategies which represents a major area of unmet need in human cancer care. Dr. Diamond has assembled a mentorship team of independently- funded, internationally-recognized investigators with expertise in breast cancer clinical trials and correlative tissue testing (Virginia Borges, MD), translational clinical trials, preclinical biomarker development and animal modeling (S. Gail Eckhardt, MD, Dan Gustafson, PhD), bioinformatics (Aik Choon Tan, PhD) and p53 signal transduction in cancer cells (Joaquin Espinosa, PhD). In conjunction with her mentorship team, the candidate has developed a detailed career development plan which will ensure that she successfully transitions to a leader in new drug development in breast cancer, capable of advancing the field and improving outcomes for patients with advanced triple-negative breast cancer.

Public Health Relevance

Triple-negative breast cancer is an aggressive breast cancer subtype that lacks treatment options that can be tailored to a particular individual's tumor characteristics. The purpose of this study is to complete a clinical trial investigating ENMD-2076, a novel Aurora and angiogenic kinase inhibitor, in patients with advanced triple-negative breast cancer. This study aims to understand how ENMD-2076 works in triple-negative breast cancer cells and to explore tumor characteristics that can predict clinical benefit from this drug.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZCA1-RTRB-E (M1))
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Lim, Susan E
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University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
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Diamond, Jennifer R; Eckhardt, S G; Pitts, Todd M et al. (2018) A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer. Breast Cancer Res 20:82
Diamond, Jennifer R; Goff, Barbara; Forster, Martin D et al. (2017) Phase Ib study of the mitochondrial inhibitor ME-344 plus topotecan in patients with previously treated, locally advanced or metastatic small cell lung, ovarian and cervical cancers. Invest New Drugs 35:627-633
Bardia, Aditya; Mayer, Ingrid A; Diamond, Jennifer R et al. (2017) Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol 35:2141-2148
Ionkina, Anastasia A; Tentler, John J; Kim, Jihye et al. (2017) Efficacy and Molecular Mechanisms of Differentiated Response to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Models of p53-Mutated Triple-Negative Breast Cancer. Front Oncol 7:94
Owsley, J; Jimeno, A; Diamond, J R (2016) Palbociclib:CDK4/6 inhibition in the treatment of ER-positive breast cancer. Drugs Today (Barc) 52:119-29
Weekes, Colin D; Lamberts, Laetitia E; Borad, Mitesh J et al. (2016) Phase I Study of DMOT4039A, an Antibody-Drug Conjugate Targeting Mesothelin, in Patients with Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer. Mol Cancer Ther 15:439-47
Tentler, John J; Ionkina, Anastasia A; Tan, Aik Choon et al. (2015) p53 Family Members Regulate Phenotypic Response to Aurora Kinase A Inhibition in Triple-Negative Breast Cancer. Mol Cancer Ther 14:1117-29
Chiorean, Elena Gabriela; LoRusso, Patricia; Strother, Robert Matthew et al. (2015) A Phase I First-in-Human Study of Enoticumab (REGN421), a Fully Human Delta-like Ligand 4 (Dll4) Monoclonal Antibody in Patients with Advanced Solid Tumors. Clin Cancer Res 21:2695-703
Ryall, Karen A; Kim, Jihye; Klauck, Peter J et al. (2015) An integrated bioinformatics analysis to dissect kinase dependency in triple negative breast cancer. BMC Genomics 16 Suppl 12:S2
Kim, Youngchul; Guntupalli, Saketh R; Lee, Sun J et al. (2014) Retrospective analysis of survival improvement by molecular biomarker-based personalized chemotherapy for recurrent ovarian cancer. PLoS One 9:e86532

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