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C. Kent Osborne, MD
Director, Dan L. Duncan Cancer Center
Professor of Medicine and Molecular and Cellular Biology
Baylor College of Medicine
Seeking to improve response to targeted therapies in advanced estrogen receptor-positive and HER2 breast cancers
Laboratory and clinical studies are ongoing to understand resistance to endocrine and anti-HER2 therapy, and develop new treatment strategies to overcome them.
These studies will lead to new clinical trials that match patients to treatments based on the molecular characteristics of each tumor.
Although 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 collaborating to develop new models of resistance that can be used in laboratory studies to identify key molecules responsible for treatment resistance and to test new treatments that will improve patient outcome
Their BCRF research suggests that drug resistance occurs because of the cooperation of compensatory and/or adaptive mechanisms that leads to the evolution of rare tumor cells with unique mutations and/or non-genetic modifications to DNA (epigenetic features). These studies have guided their discovery of several new drug combinations.
They have also identified several resistance mechanisms to anti-HER2 therapies, which include an increase in the activity of the cholesterol synthesis and the ER pathways, mutations in the HER2 protein itself, increased levels of other signaling molecules, and alterations in various components of the patient's immune system.
Over the next year, the team will continue to develop and characterize new drug-resistant preclinical models, including a laboratory model of metastatic breast cancer. They will use these as well as clinical breast tumor samples to investigate known resistance mechanisms, identify new drivers of resistance to endocrine and anti-HER2 therapy, and develop new treatment strategies to overcome them. They hope to develop a clinical test to identify patients with HER2+ disease who can be spared chemotherapy.
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 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.