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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 in laboratory models of triple negative breast cancer.
- This study could advance a promising targeted therapy to benefit patients with this aggressive disease.
Triple negative breast cancer is an aggressive disease for which there are no approved targeted therapies. While targeted approaches are being developed and tested, chemotherapy remains the most effective strategy in treating TNBC. The development of drug resistance is common, however. Dr. Miller is conducting laboratory and clinical studies to test combination targeted approaches to make triple negative breast cancers more sensitive to current therapies.
Full Research Summary
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. Currently the standard treatment from TNBC is chemotherapy and many tumors will develop resistance to the common chemotherapy agents.
The goal of Dr. Miller’s BCRF research is to identify novel combinations to effectively kill triple negative breast cancer cell and improve response to chemotherapy.
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.
Last year, the team initiated a Phase I clinical trial of a drug that blocks PI3K called Gedatolisib, and a drug that targets the Wnt pathway called PTK7-ADC (NCT03243331). They have enrolled four patients, and two of them are showing improvements. The treatment is well tolerated. The primary goal of this trial is to determine the safety of this combination. Further studies using tissue and blood samples from patients in this trial will aim to identify biomarkers that can predict which patients are most likely to benefit from this therapy.
The team is also investigating whether adding the heartburn medication, omeprazole to chemotherapy will improve tumor response to treatment. The team is performing a clinical study in which omeprazole is added to chemotherapy as initial therapy. The clinical trial is now open at four centers around the country (NCT02595372). Early data from tumor samples collected in that trial suggest that the ulcer drug inhibits the enzyme as predicted.
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.