Mount Sinai Researchers Create RNA and DNA-Sequencing Platform to Match Broader Swath of Cancer Drugs to Patients With Few Options
A comprehensive RNA and DNA sequencing platform benefits late-stage and drug-resistant multiple myeloma patients by determining which drugs would work best for them, according to results from a clinical trial published in JCO Precision Oncology in August.
The novel platform, created by Mount Sinai cancer, genomics, and precision health researchers, expands on traditional DNA-based approaches by using RNA sequencing to find targets for a broad swath of FDA-approved cancer drugs beyond those approved specifically for multiple myeloma. This approach was tested in a pilot precision medicine clinical trial with 64 patients with late-stage and drug resistant multiple myeloma, the second most common blood cancer. All of the patients had run out of other treatment options.
“Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients,” said researcher Samir Parekh, MD, Associate Professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences and Director of Translational Research in Myeloma at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. “The trial has allowed us to test the accuracy of our platform, laying the foundation for our next-generation precision medicine framework.”
The results of this study showed that a comprehensive approach that includes RNA sequencing can provide more treatments for patients with advanced disease beyond the standard DNA analysis currently available. A majority of the patients in the trial received a drug based on their cancer’s RNA profile and many benefited from their personalized treatment plans.
“Current approaches in precision oncology aim at matching specific DNA mutations to drugs, but incorporation of genome-wide RNA profiles had not been clinically assessed before now,” said researcher Alessandro Lagana, PhD, Assistant Professor of Genetics and Genomic Sciences at the Institute for Next Generation Healthcare and the Icahn Institute for Genomics and Multiscale Biology at the Icahn School of Medicine at Mount Sinai. “We expect RNA sequencing will play a larger role in the precise delivery of targeted drugs in oncology.”
Mount Sinai researchers have already received funding to develop a next-generation clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan.
“This research is part of an accelerating paradigm shift in cancer therapy, where treatment may be given based on the specific genomic alterations observed in a patient’s tumor, rather than on the tumor histology or tissue type,” said Joel Dudley, PhD, Executive Vice President for Precision Health, Director of the Institute for Next Generation Healthcare, and Associate Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. “RNA sequencing will likely complement current precision medicine strategies in the near future due to its ability to capture more dynamic aspects of unique tumor biology and provide information beyond what is capable with DNA alone.”
The study was supported by funds from a National Institutes of Health/National Cancer Institute grant (R21: 1R21CA209875-01A1), The Tisch Cancer Institute at Mount Sinai’s National Cancer Institute Support Grant (P30 CA196521) and the Multiple Myeloma philanthropic fund.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and the South Nassau Communities Hospital is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.