• Press Release

Researchers Identify New Drug Target for Blood Cancer, Potentially Solid Tumors

Findings are being used to create a clinical trial for patients with myelodysplastic syndrome

  • New York, NY
  • (October 07, 2021)

Mount Sinai and UC San Diego researchers have shown for the first time how mutations affecting a cellular process called RNA splicing alter cells to develop myelodysplastic syndrome (MDS) and other hematologic malignancies and solid tumors, according to a study published in Cancer Discovery in October.

Their research found that these mutations produce an alternative version of the protein created by the gene GNAS. This protein can be targeted by drugs already approved by the Food and Drug Administration for treating other cancers, and therefore could be a good target in MDS. The researchers are creating a clinical trial to test these drugs, known as MEK inhibitors and named for the proteins they inhibit to stop cancer.

MDS is a rare blood cancer that has no effective treatments and a poor prognosis. The mutations investigated in this study, however, are also found in other cancers, which extends the possible applications of these findings.

 “This is the first study to discover that the altered protein created by GNAS is increased in cells with these mutations in MDS, and this results in the activation of processes that would render the cancer cells vulnerable to the MEK inhibitors,” said co-senior author Eirini Papapetrou, MD, PhD, Associate Professor of Oncological Sciences at The Tisch Cancer Institute. “The discovery that we can try to use MEK inhibitors in this cancer is also a first, and our findings also support future drug development to target GNAS, identified in this study.”

Papapetrou led the study with Gene Yeo, PhD, professor at UC San Diego School of Medicine. The researchers generated models of the mutations using stem cells, in order to study them in a physiological genetic context. They then turned the engineered cells into hematopoietic progenitor cells—which are the relevant cell type in blood cancers—and performed splicing and RNA binding analyses.

“This work integrates isogenic models of disease with cutting-edge RNA-omics to converge onto a new target for MDS,” Yeo said.

These analyses allowed the team to identify high-confidence targets and to identify the driver of the disease. The team showed that MDS cells from the model as well as cells from MDS patients with these mutations were sensitive to treatment with MEK inhibitors.


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.

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