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C. Kent Osborne, MD
Director, Dan L. Duncan Comprehensive Cancer Center
Professor of Medicine and Molecular and Cellular Biology
Baylor College of Medicine
Goal: To improve response to targeted therapies in advanced estrogen receptor (ER)-positive and HER2-positive breast cancers.
Impact: Drs. Osborne and Schiff have developed a growing panel of experimental models of drug resistance and metastasis, as well as data from clinical specimens—valuable resources to advance the understanding of the underlying causes of drug resistance. Their work is paving the way for new strategies to overcome resistance and improve patient outcomes.
What’s next: The team will continue to expand their drug-resistant preclinical models, including laboratory models of resistance to a class of drugs called CDK4/6 inhibitors, endocrine therapy, and HER2 therapy.
Patients with breast cancers that have abundant levels of the estrogen receptor (ER) or the HER2 protein have several treatment options, which include targeted therapies with or without chemotherapy. However, many will be resistant or develop resistance to one or more of these drugs during their therapy, which leads to disease progression and metastasis. Drs. Osborne and Schiff are developing laboratory models that will help them understand the mechanisms of resistance, thus allowing them to identify new treatments or new combinations that can prevent or reverse drug resistance.
Full Research Summary
Research area: To identify key molecules responsible for breast cancer treatment resistance and to test new treatments that will improve outcomes.
Impact: While effective treatments for estrogen receptor (ER)-positive and HER2-positive breast cancers are available, many tumors are or become resistant to these therapies. Drs. Osborne and Schiff are conducting laboratory and clinical studies to understand resistance to endocrine and anti-HER2 therapy and develop new treatment strategies to overcome it.
Current investigation: Drs. Osborne and Schiff are developing new models of resistance and metastasis that can be used in laboratory studies to identify key molecules involved in treatment resistance and to test new drugs that will prevent or treat resistant/metastatic disease.
What they’ve learned so far: The team is continuing to grow their large panel of breast cancer models to study resistance to endocrine and/or CDK4/6 therapy and anti-HER2 therapy. They recently discovered the potential role of the immune system in resistance to CDK4/6 inhibitors, which can be overcome by repurposing existing drugs. Drs. Osborne and Schiff also revealed a cholesterol producing pathway that has a role in anti-HER2 resistance.
What’s next: The team will continue to further expand their panel of diverse breast cancer models made resistant to clinically relevant drug combinations and continue to molecularly and functionally characterize them. In particular, Drs. Osborne and Schiff will continue focusing on their recently developed endocrine, CDK4/6, and anti-HER2 therapy-resistant models.
Dr. Osborne was born in St. Louis, Missouri and received his AB and his MD from the University of Missouri, both with honors. He completed his internship and residency at Johns Hopkins and followed this with three years as a Clinical Associate at the Medicine Branch of the National Cancer Institute. He was a faculty member at the University of Texas Health Science Center from 1977 until 1999 and became Chief of Medical Oncology in 1992. In 1999, Dr. Osborne moved to Baylor College of Medicine to direct a new Breast Center and in 2004 he, in addition, was named Director of the Dan L. Duncan Comprehensive Cancer Center at Baylor.
Dr. Osborne's research interests have focused on the biology and treatment of breast cancer. He has published extensively on the role of growth factors in breast cancer pathogenesis, and he has also investigated the mechanisms of action and resistance to ER and HER2 targeted therapies in breast cancer. Dr. Osborne currently directs the Baylor Breast Cancer Specialized Program of Research Excellence Grant. Dr. Osborne has authored more than 400 manuscripts dealing with the biology and treatment of breast cancer.