While scientists have long studied mutations of the RAS oncogene as a target for new cancer drugs, they have been unable to pinpoint a drug that safely blocks its effects. Now, a team from the University of Illinois at Chicago (UIC) has identified a monobody that can block the oncogene’s activity.
RAS mutations appear in almost 30% of all cancers, according to a statement. 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.
The UIC researchers took a different tack: “We did not look for a drug or specifically for an inhibitor,” said John O’Bryan, an associate professor of pharmacology at the UIC College of Medicine, in the statement. “We used monobody technology, a type of protein-engineering technology, to identify regions of RAS that are critical for its function.”
The team found that a synthetic binding protein, dubbed the NS1 monobody, was able to inhibit RAS protein activity. Monobodies have been used to target a variety of proteins, such as enzymes and cell receptors, according to the statement. Unlike regular antibodies, O’Bryan said, monobodies are not dependent on their environment and can be used as genetically encoded inhibitors. When a monobody binds to a protein--in this case, RAS proteins--it generally acts as an inhibitor of that protein, he said.
The NS1 monobody works by binding to a spot on the RAS protein molecule, thereby inhibiting its oncogenic activity, according to the statement. It blocks the oncogenic function of two out of the three RAS proteins by preventing the protein from joining an identical molecule to form a pair.
While further studies and trials are required before moving the monobody out of the lab, the findings could lead to new therapies for various cancers that work by targeting mutant RAS activity in cancer cells. This could be especially important for melanoma, the deadliest of the skin cancers, and for pancreatic cancer, of which a diagnosis can often mean a death sentence.