James M. Rae, PhD
Ann Arbor, Michigan
Thomas H. Simpson Collegiate Professor in Cancer Research
Associate Professor of Pharmacology
Identifying inherited genetic markers that will be able to predict whether an individual patient will respond to and tolerate specific anti-estrogen breast cancer therapies.
Approximately 70 percent of breast cancer patients have estrogen-receptor (ER)-positive disease and will receive some form of endocrine therapy (ET), such as tamoxifen and aromatase inhibitors. However, only approximately 60 percent of these patients will benefit, and 30 percent will experience severe side effects that result in suspension of treatment. Dr. Rae and his team are searching for inherited gene variants that can be used to identify which patients will benefit from ET. Their findings could lead to more precise selection of the optimal type of ET, which will improve treatment adherence while reducing the likelihood that patients will experience treatment-related side effects.
Dr. Rae's team collects tumor tissue and blood samples from a broad array of clinical trials that study the treatment of ER-positive breast cancer. The value in using samples from multiple studies includes the large number of patients analyzed, the long-term and detailed clinical follow-up data, the inclusion of control groups, and the ability to validate findings across the different patient cohorts. The team recently uncovered several genetic changes associated with patients discontinuing their ET due to musculoskeletal side effects. They also performed a study in aromatase inhibitor-treated breast cancer where they uncovered genetic variants associated with patients’ pain thresholds.
Dr. Rae’s team will continue to explore genetics-based methods to identify the optimal therapy for individual patients. They are sifting through the data of several large clinical trials and leveraging a national network of collaborators to further support existing findings and identify new genetic associations with treatment response. There are several studies that are nearing completion and the results obtained will provide key data needed to identify new genetic variants of interest.
Dr. Rae received a BS in biology from the University of Pittsburgh and PhD in pharmacology from Georgetown University. In graduate school, he combined his interest in breast cancer research with cutting-edge aspects of pharmacology including personalized medicine which uses a patient’s unique genetic makeup to guide treatment decisions. He moved to the University of Michigan in 2001 where he rose to the rank of Associate Professor (with tenure) in the Department of Internal Medicine and holds a joint appointment in the Department of Pharmacology. Dr. Rae’s principal expertise is in the area of cancer drug metabolism, pharmacogenetics/genomics, translational oncology, biomarker identification and characterization, and estrogen receptor signaling, particularly as these may apply to the prediction of breast cancer treatment response. His current research focuses on identifying the subset of estrogen receptor positive breast cancer patients who will respond to endocrine therapy. His work involves two major lines of investigation; one attempts to predict patient response to therapy using a pharmacogenetics approach, while the other seeks to identify and characterize the role of steroid hormone signaling in the growth regulation of breast cancer and the molecular and cellular biology of malignant progression. His work in pharmacogenetics, the study of genetic variability in the way patients respond to medications, involves studies with tamoxifen and aromatase inhibitors and the use of genetic testing to identify patients likely to respond to therapy.
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