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James M. Rae, PhD

Associate Professor of Internal Medicine and Pharmacology
Thomas H. Simpson Collegiate Professorship in Cancer Research
University of Michigan
Ann Arbor, Michigan

Current Research

Goal: To understand how a patient’s unique genetic makeup can be used to determine whether she will benefit from specific breast cancer therapies.

Impact: Dr. Rae has been analyzing tumor tissue and blood samples from thousands of patients enrolled in a number of large breast cancer clinical trials. They aim to discover genetic predictors of treatment response to and toxicities of anti-estrogen therapies, which will lead to personalized treatment decisions.

What’s next: The team will continue correlating the genetic makeup of patients with ER-positive breast cancer with response to treatment and side effects.

Most breast cancers require estrogen to grow and can be treated with anti-estrogen therapies such as tamoxifen or aromatase inhibitors. However, not all women with ER-positive breast cancer respond to these medications, and some may experience unwanted side effects. Dr. Rae is analyzing patient samples from large clinical trials to understand how inherited genetic factors can affect the tolerance of or response to various types of anti-estrogen drugs.

Full Research Summary

Research area: 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. 

Impact: Anti-estrogen drugs such as tamoxifen and aromatase inhibitors (AIs) have dramatically improved outcomes in patients with estrogen receptor (ER)-positive breast cancers. But not all women with ER-positive tumors respond to these therapies, and some may experience a cancer recurrence after treatment. Still others may experience toxicities to these therapies. Dr. Rae is focused on identifying inherited gene variants that can be used to identify which patients will benefit from endocrine therapy (ET). Their findings could lead to more precise selection of the optimal type of ET and improve treatment adherence to these lifesaving drugs by identifying patients most likely to experience treatment-related side effects. 

Current investigation: Dr. Rae’s team has been genotyping patients enrolled into a number of prospective, randomized clinical trials that have established the role of endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer. The value in using samples from multiple prospective 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.

What they’ve learned so far: Dr. Rae has identified a novel gene that predicts when a patient may be at risk of endocrine therapy-related toxicity. His studies continue to inform genetic-based methods of selecting the optimal type of therapy for individual patients. 

What’s next: Dr. Rae will continue ongoing genetic analyses of multiple patient cohorts and complete the statistical analyses needed to validate important pharmacogenomic discoveries that have the potential to impact breast cancer treatment.

Biography

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.

Grid Researcher Headshot - Rae J

BCRF Investigator Since

2008

Donor Recognition

The Macy's Award