Researchers find novel way to inhibit major cancer gene

Researchers have identified a new way to block the action of genetic mutations found in nearly 30 per cent of all cancers.

Mutations in genes for the RAS family of proteins are present in nearly 90 per cent of pancreatic cancers and are also highly prevalent in colon cancer, lung cancer and melanoma, the most dangerous kind of skin cancer.

"We did not look for a drug or specifically for an inhibitor," said John O'Bryan, Associate Professor at University of Illinois College of Medicine in the US.

"We used monobody technology, a type of protein-engineering technology, to identify regions of RAS that are critical for its function," O'Bryan said.

Unlike conventional antibodies, monobodies are not dependent on their environment and can be readily used as genetically encoded inhibitors, O'Bryan said.

"The beauty of the technology is that when a monobody binds a protein, it usually works as an inhibitor of that protein," he said.

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.

The researchers discovered that a synthetic binding protein they call "NS1 monobody," which they created in the lab, can block the activity of the RAS proteins.

The findings, published in the journal Nature Chemical Biology, provide important insight into long-standing questions about how RAS proteins function in cells.

"Development of effective RAS inhibitors represents a 'holy grail' in cancer biology," O'Bryan said.

"We now have a powerful tool we can use to further probe RAS function. 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 tumour growth," he added.

--IANS

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