• 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

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2023-2024.

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