Director, Dan L. Duncan Cancer Center
Professor of Medicine and Molecular and Cellular Biology
Baylor College of Medicine
Co-Investigator: Rachel Schiff, PhD, Baylor College of Medicine, Houston
Effective targeted treatments against the estrogen receptor-positive (ER+) and HER2+ breast cancers are currently available in the clinic, but tumor resistance is common. The goals of Drs. Osborne and Schiff’s studies are to continue to characterize new models of resistance that will allow for genomic, molecular, and therapeutic studies aiming to identify key molecules responsible for treatment resistance and to develop new treatment strategies that will improve response and patient outcome. In 2013-2014 Drs. Schiff and Osborne will continue to identify most effective drug combinations with a focus on novel inhibitors of kinase proteins activated by growth factor signaling and new agents, called SERDS, that can degrade the ER protein (SERDs). They will further investigate compensatory and feedback signaling induced in tumors in response to these drugs in order to understand how to prevent the acquisition a secondary resistance. The role of a few new potential genes in resistance to antiHER2 therapies will also continue to be explored.
Recent findings by Drs. Osborne and Schiff now suggest that both more common compensatory and adaptive mechanisms as well as the evolution of rare clones with unique (“personalized”) genomic and/or epigenomic features of resistance co-operate during the emergence of drug resistance. Specifically, they have identified a switch in ER activity that can stem from genetic aberrations and over-expression of ER co-regulators using models of endocrine resistance. Consequently, a specific set of cytokines known to regulate tumor survival and metastasis are induced. Inhibition of either the aberrant ER co-regulators or the cytokines can inhibit tumor cell growth and overcome resistance. Similarly, their studies also have identified unique genetic aberrations in resistance models to potent HER2-targeted therapies, including mutations in the HER2 receptor itself. The researchers will continue to characterize the adaptive and selected resistant mechanisms that operate in their resistant models, which represent genetic diversity of tumors in the clinic, and to identify new strategies and effective drug combinations to overcome them. Their recent studies also support the efficacy of a new oral compound that can degrade the ER protein (SERDs) and overcome tamoxifen resistance. They will continue to evaluate this drug and its mechanism of action with the goal to provide sufficient evidence for its clinical development.
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 at Baylor College of Medicine 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 tamoxifen action and resistance in breast cancer. As previous Chairman of the Breast Cancer Committee for the Southwest Oncology Group, he directed numerous clinical trials investigating new treatment strategies in primary and metastatic breast cancer. Dr. Osborne currently directs the Baylor Breast Cancer Specialized Program of Research Excellence Grant. Dr. Osborne has authored more than 350 manuscripts dealing with the biology and treatment of breast cancer.