Newswise — New York, NY (June 15, 2022) — Mount Sinai researchers have for the first time identified genes that predict a good response to a vital new therapy for a blood cancer that can have serious side effects for some patients.

The therapy, selinexor, is part of many groundbreaking therapies for the blood cancer multiple myeloma, but the ability to target its use to patients who would benefit the most remained elusive until now, according to a study published in JCO Precision Oncology in June.

The Mount Sinai scientists sequenced RNA of multiple myeloma tumors from patients treated with selinexor and identified a signature of three genes that were activated in patients who had positive responses. They validated the signature in an independent group of patients who participated in an international clinical trial that led to Food and Drug Administration (FDA) approval of the drug.

“This signature has important clinical significance, as it could identify patients who are most likely to benefit from treatment with selinexor-based therapy, especially in earlier lines of therapy,” said one of the senior authors, Alessandro Lagana, PhD, Assistant Professor of Oncological Sciences at The Tisch Cancer Institute at Mount Sinai and Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.

Samir Parekh, MD, Director of Translational Research in Myeloma at The Tisch Cancer Institute at Mount Sinai, the other senior author of the study, added, “Our findings provide the basis for improving patient selection for targeted agents using a small panel of genes to guide precise application of these drugs in real world scenarios, including relapse following CAR-T, an increasingly important clinical challenge in Myeloma.”

Selinexor has proven helpful for patients who failed other FDA-approved therapies for multiple myeloma. However, the majority of patients who take the drug experience side effects, sometimes severe, so it is important to identify patients who will respond positively and potentially expand the use of the drug into patients who haven’t failed other therapies.

Mount Sinai researchers identified the three genes, WNT10A, DUSP1, and ETV7, by sequencing the tumors of about 100 multiple myeloma patients who received the drug. They also found the three-gene signature in patients with the brain cancer glioblastoma who responded well to selinexor.

As a result of this study, Mount Sinai has begun to further study tests for this signature to identify patients who may benefit from selinexor in patients who qualify to use the drug as well as patients who participate in a precision medicine clinical trial launching soon.

 

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. 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 "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

For more information, visit https://www.mountsinai.org or find Mount Sinai on FacebookTwitter and YouTube.