Mount Sinai Researchers Discover Genes That Predict Good Response to Blood Cancer Therapy
Patients whose multiple myeloma has three-gene signature are likely to benefit
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
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.
