Dr. Brodie is the 2005 recipient of the Kettering Prize from the General Motors Cancer Research Foundation (GMCRF) and was awarded the 2006 Dorothy P. Landon-AACR Prize for Translational Cancer Research for her groundbreaking work in developing aromatase inhibitors, a new class of breast cancer drugs.
A primary focus of our research has been on the enzyme aromatase. Because of its key role in estrogen biosynthesis, we have investigated aromatase as a target for developing potent and selective inhibitors and their use in the treatment of breast cancer. This has led to a new class of agents for breast cancer treatment and three compounds are now approved for use by the FDA. We are currently studying strategies to optimize the efficacy of these agents and estrogen receptor antagonist based on molecular mechanisms in order to improve the treatment of breast cancer and also to prevent breast cancer. We have developed unique model systems using aromatase transfected cells to determine the effects of these agents on gene expression in proliferation and apoptosis as well as on adaptive changes, such as modulation of the estrogen receptor and steroid co-activators which occur during treatment with aromatase inhibitors and antiestrogens. In prostate cancer research, we have recently patented a number of novel compounds that inhibit androgen synthesis as well as androgen action as potential new therapies. Current studies are determining the interaction of these compounds with the androgen receptor and its mutations, their effects on cancer cell proliferation and apoptosis in vitro and in animal models.
Lab Techniques and Equipment:
• Steroid enzyme and receptor assays
• ELISA and radioimmunoassays
• Cell cultures
• Cell transfections
• PCR, Northern and Western blots
• In vivo tumor models
Gregory Klus, Ph.D., Research Associate, Uniformed Army Services University, Bethesda, MD.
Wei Yue, MD, Ph.D., Research Assistant Professor, University of Virginia Medical School, Charlottesville,VA.
Dmitry Grigoryev, Ph.D., Postdoctoral Training Program in Cancer Research (Dr. Ira Pastan) NCI, Bethesda, MD.
Ivo Nnane, Ph.D., Assistant Professor, Temple University, Philadelphia, PA.
Qing Lu, MD, Ph.D., Residency Program, University of Pennsylvania, Philadelphia, PA.
Jisong Li, M.D., Staff Scientist, Pfizer Pharmaceuticals, Groton, CT.
Education and Training:
• B.Sc.(with honors), Sheffield University, UK
• Ph.D., Manchester University, UK
• NIH Fellowship in Steroid Biochemistry, Clark University, MA
Brodie AMH, Schwarzel WC, Shaikh AA, Brodie HJ: The Effect of an Aromatase Inhibitor, 4-Hydroxy-4-Androstene-3,17-Dione, on Estrogen Dependent Processes in Reproduction and Breast Cancer. Endocrinology, 100:1684-1695, 1977.
Coombes CR, Goss P, Dowsett M, Gazet JC, Brodie A: 4-Hydroxyandostenedione in Treatment of Postmenopausal Patients with Advanced Breast Cancer. Lancet, 2:1237-1239, 1984
Goss PE, Coombes RL, Powles TJ, Dowsett M, Brodie AMH: Treatment of Advanced Postmenopausal Breast Cancer with Aromatase Inhibitor, 4-Hydroxyandrostenedione-Phase 2 Report. Cancer Res, 46:4823-4826, 1986.
Njar VCO, Brodie AMH: Inhibitors of 17á-Hydroxylase/C17,20-Lyase (CYP17): Potential Agents for the Treatment of Prostate Cancer. Current Pharm Design, 5:163-180, 1999
Nnane IP, Kato K, Liu Y, Long BJ, Lu Q, Wang X, Ling YZ, Brodie AMH: Inhibition of Androgen Synthesis in Human Testicular and Prostatic Microsomes and in Male Rats by Novel Steroidal Compounds. Endocrinology, 140:2891-2897,1999
Long B, Grigoryev D, Nnane I, Liu Y, Ling YZ, Brodie A: Antiandrogen Effects of Novel Inhibitors of Androgen Synthesis Inhibitors on Hormone-dependent Prostate Cancer. Cancer Res, 60:6630-6640, 2000.
Brodie A: Aromatase Inhibitors and the Application to the Treatment of Breast Cancer. In: Breast Cancer: Prognosis, Treatment and Prevention, ed. Jorge Pasqualini, Chapter 8, pp. 251-270, 2002, Marcel Dekker, NY.
Long BJ, Jelovac D, Handratta V, Thiantanawat A, MacPherson N, Ragaz J, Brodie AM: Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model. JNCI 96:456-465,2004.