Robert Orlowski, M.D., Ph.D., is Chairman, Ad Interim, Director of Myeloma and Professor of Medicine in the Departments of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, where he is also a Professor of Experimental Therapeutics in the Division of Cancer Medicine. His clinical research efforts focus on the translation of promising laboratory-based findings into novel clinical trials for patients with hematologic malignancies. Dr. Orlowski is collaborating with Arvinas to analyze the activity of BET PROTACTM protein degraders
in established and patient-derived cell line models of multiple myeloma, and has demonstrated that BET PROTAC protein degraders exert inhibitory effects on the growth of drug-resistant myeloma cells. He has shown that BET PROTAC protein degraders reduce the viability of primary myeloma cells from patients with relapsed or refractory multiple myeloma. These data were discussed as part of an oral presentation by Dr. Orlowski at The American Society of Hematology’s Annual Meeting in 2015.
Gautam Borthakur, M.D. is an Associate Professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Dr. Borthakur’s preclinical research is focused on the characterization of promising novel therapeutics for the treatment of hematological malignancies. Arvinas is collaborating with Dr. Borthakur to examine the impact of BET PROTAC protein degraders on in vitro proliferation, differentiation and apoptotic programs in cell lines that overexpress c-MYC and primary samples from patients with AML, ALL and CLL. Dr. Borthakur has demonstrated that BET PROTAC protein degraders cause a higher degree of apoptosis in primary AML blasts than the BET inhibitor JQ1. This data was discussed as part of an oral presentation by Dr. Borthakur at the American Society of Hematology’s Annual Meeting in 2015.
Kapil Bhalla M.D., F.A.C.P., is a Professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. The focus of the basic and translational research in Dr. Bhalla’s laboratory includes the biology and developmental therapeutics related to epigenetic mechanisms involving histone deacetylases, methyltransferases and demethylases, BET proteins, as well as the chaperone biology of heat shock proteins and their cancer relevant client proteins regulating cell growth, differentiation and survival of the human leukemia stem/progenitor cells. Arvinas is collaborating with Dr. Bhalla to compare the activity of BET PROTAC protein degraders and BET inhibitors in established and patient derived leukemia and lymphoma cells. HR has demonstrated that BET PROTAC protein degraders deplete the BET proteins BRD4 and BRD3 and lead to greater attenuation of BRD4 target genes and greater in vitro and in vivo lethality in Mantle Cell Lymphoma (MCL) patient-derived xenograft cells. This work will be presented as a podium presentation at The American Society of Hematology’s Annual Meetings in San Diego in December 2016.