Researchers have identified a new way to block the action of genetic mutations found in nearly 30 percent of all cancers.
Mutations in genes for the RAS family of proteins are present in nearly 90 percent of pancreatic cancers and are also highly prevalent in colon cancer, lung cancer and melanoma, the most dangerous kind of skin cancer.
The group of proteins include three members, K-RAS, H-RAS and N-RAS.
The prevalence of RAS mutations in human cancers and the dependence of tumors on RAS for survival has made a RAS a prime target for cancer research and drug discovery. Scientists and drug developers have long studied RAS oncogenes hoping to find a new treatment for cancer, but they have not yet been able to identify drugs that safely inhibit the oncogene's activity.
Researchers took a different approach to studying RAS, and discovered that a synthetic binding protein they call "NS1 monobody," which they created in the lab, can block the activity of the RAS proteins.
Unlike conventional antibodies, monobodies are not dependent on their environment and can be readily used as genetically encoded inhibitors, author said.
The researchers found that the NS1 monobody binds to an area of the RAS protein molecule (allosteric site) that was not previously known to be important for its oncogenic activity. NS1 strongly inhibits oncogenic K-RAS and H-RAS function by blocking the ability of the protein to interact with an identical one to form a molecular pair. NS1 does not affect N-RAS.
The findings published in the journal Nature Chemical Biology, provide important insight into long-standing questions about how RAS proteins function in cells. These insights may help guide the development of new therapeutic approaches to treating cancer by interfering with mutant RAS function in cancer cells.
While future studies and trials are needed before these findings can be leveraged outside the lab, this study provides new insight into how we can potentially inhibit RAS to slow tumor growth."
Monoclonal antibody against cancer mutant protein Ras developed!
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