UIC researchers identify new way to inhibit major cancer gene

RAS mutations appear in about 30% of all cancers. They are also present in nearly 90% of pancreatic cancers and occur frequently in colon cancer, lung cancer and melanoma.

There are three RAS proteins: K-RAS, H-RAS and N-RAS.

During their research, the scientists created a synthetic binding protein in the lab, dubbed NS1 monobody and found that it can inhibit the RAS proteins.

O’Bryan said that the team did not look for a drug or particularly for an inhibitor. He added that the team had used a type of protein-engineering technology called as monobody technology to identify RAS regions 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.

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

RAS is said to be a prime target for cancer research and drug discovery owing to its mutations and the dependence of tumors on it for survival.

In the research, it was found out that the NS1 monbody binds to an RAS protein molecule area that was not known before to be important for its oncogenic activity. The monobody stops the function of oncogenic H-RAS and K-RAS by blocking the protein’s ability in its interaction with another identical protein to form a molecular pair.

The researchers found that N-RAS remained unaffected by the NS1 monobody.

O’Bryan concluded that the new insights could help in the development of new therapeutic methods for cancer treatment by the interference of mutant RAS function in cancer cells by the NS1 monobody.

Image: Monobody NS1 binds to H-RAS or K-RAS protein and blocks RAS function by disrupting the protein’s ability to form active molecular pairs. Photo: courtesy of The Board of Trustees of the University of Illinois.