In our fourth MCRI episode featuring the top 10 proposals for high-risk multiple myeloma, Dr. Robert Orlowski of the MD Anderson Cancer Center teaches us about the aggressive nature of del17p. He explains that when patients have del17p, they lose an important gene (p53) that typically is the "defender of the genome" that keeps genetic mutations in check. P53 is THE most commonly mutated gene across all cancers. When that gene is lost or mutated, cancer cells can grow exponentially because they are no longer properly regulated by this master regulator gene. They have found that when this p53 gene is mutated, a protein called survivin is found in higher quantities. Survivin helps keep myeloma cells alive, which is why traditional chemotherapies don't work exceptionally well for those with del 17p. By targeting this survivin protein with an inhibitor, or "designer drug" just for this problem, then the traditional drugs like bortezomib and pomalidomide can be used to kill the myeloma cells without resistance issues. The survivin inhibitor has already been tested in Phase I clinical trials but this is the first time that it is being used with combination therapies in multiple myeloma for a one-two punch at myeloma cells.
Robert Z. Orlowski, M.D., Ph.D., is Director of Myeloma, and Professor of Medicine in the Departments of Lymphoma/Myeloma and Experimental Therapeutics, where he is board-certified in medical oncology. Dr. Orlowski earned his doctoral degree in molecular biophysics and biochemistry from Yale University and his medical degree from the Yale University School of Medicine. He completed his internship and residency in Internal Medicine at Barnes Hospital at the Washington University in St. Louis School of Medicine. After his fellowships in Hematology and Medical Oncology at John Hopkins Sidney Kimmel Comprehensive Cancer Center, he joined the faculty at University of North Carolina in Chapel Hill. Following that, Dr. Orlowski accepted a position at The University of Texas MD Anderson Cancer Center in 2007 to lead the Myeloma Section in the Department of Lymphoma/Myeloma. His research interests include pathobiology of, novel therapeutic targets and mechanisms of drug resistance in myeloma which are documented in hundreds of scientific articles, book chapters, and presentations at conferences. Dr. Orlowski is an investigator on numerous clinical trials, and appointed Myeloma Committee Chair for SWOG.
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical research. Founder of the HealthTree Foundation.
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