Dr Mitsiades’ research focuses on developing novel therapies which neutralize the ability of tumor cells from multiple myeloma (MM), other blood cancers or metastatic solid tumors to develop resistance to pharmacological and immune therapies. Toward this goal, Dr Mitsiades and his lab have been developing preclinical models to simulate more accurately the biological behavior and treatment response vs. resistance of tumor cells as they interact with nonmalignant cells of their local tissues. Dr. Mitsiades’ work documented that nonmalignant "accessory" cells of the tumor microenvironment (e.g bone marrow stromal cells) can decrease the sensitivity of MM and solid tumors to diverse drug classes and immune effector cells. His lab also defined distinct mechanisms regulating the treatment response vs. resistance of solid tumor cells within their 3-dimensional architecture and how tumor cells can develop reversible persistence to diverse types of chemotherapeutics. With these models and CRISPR-based functional genomic studies, Dr Mitsiades’ studies have been defining the mechanisms through which MM or other tumors develop resistance to established/investigational drugs or immunotherapies, determining the molecular "drivers" of MM cells, particularly those with treatment resistance, and designing rational combinations of established or novel therapies to overcome, delay or prevent treatment resistance. The preclinical studies of Dr. Mitsiades have informed the design of several regimens which are now FDA-approved, represent a standard-of-care for MM treatment or demonstrated promising activity in clinical trials. Several of these regimens contributed to the increased overall survival of MM patients in the last decade and are a "backbone" for combination with other novel agents, such as monoclonal antibodies. Dr Mitsiades' studies established that inhibition of BET bromodomain proteins, such as BRD4, suppress the function and expression of the oncoprotein c-Myc, leading to major interest for BET bromodomain inhibition in MM and other cancers.
Constantine S. Mitsiades, MD, PhD