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Kathy D. Miller, MD
Ballve Lantero Scholar in Oncology
Professor, Department of Medicine
Co-Director, Simon Cancer Center Breast Cancer Program
Indiana University School of Medicine
Seeking to improve outcomes for patients with triple negative breast cancer by identifying potential new drug targets and combination therapies.
A clinical trial is planned to test a dual targeted therapy that was very effective at killing tumors in laboratory models of triple negative breast cancer.
If this strategy proves successful in clinical trials, it could advance a promising targeted therapy to benefit patients with this aggressive disease.
Triple negative breast cancer (TNBC) accounts for 15-20 percent of all breast cancer cases in the United States, and despite its lower incidence, contributes to a disproportionately higher rate of mortality compared to other breast cancer subtypes. Because these tumors lack the estrogen, progesterone, and HER2 receptors (“triple-negative”), successful treatments against these cellular targets are not effective in TNBC.
Recent advances in understanding the genomics of TNBC have uncovered a survival pathway called PI3K that promotes TNBC growth and survival. This pathway is highly active in most TNBC tumors, yet targeted therapies do not always elicit a positive response.
TNBCs can overcome PI3K-targeted drugs by activating other pro-survival machinery, including the Wnt pathway. Dr. Miller and her team recently demonstrated that when both the PI3K and Wnt pathways are targeted simultaneously in laboratory models, a synergistic anti-tumor response occurs.
In the coming year, the team will perform a Phase I clinical trial of a drug that blocks PI3K called Gedatolisib, and a drug that targets the Wnt pathway called PTK7-ADC. The primary endpoint of this trial is to determine the safety of this combination. Further studies using samples from this trial will aim to identify predictive biomarkers of response to this therapy.
Kathy D. Miller received her MD in 1991 from the Johns Hopkins School of Medicine in Baltimore, MD. Dr. Miller completed internal medicine training at Hopkins, then returned to her native Midwest for fellowship training at Indiana University, serving as Chief Fellow in 1997. She returned to Indiana University in 1999, attaining the rank of Professor and Ballvé-Lantero Scholar in 2014.
Dr. Miller’s career has combined both laboratory and clinical research in breast cancer. She became chair of the ECOG-ACRIN Breast Core Committee in January 2014. In this role she works with academic scientists and community oncologists to develop trials that combine clinical and biologic endpoints yet remain feasible in non-academic settings. Dr. Miller honed her ability to coordinate multi-center trials as principal investigator for three previous ECOG trials. In addition, she serves as principal investigator of the National Clinical Trials Network at Indiana University.