In the continual search for an effective way to stop lung cancer from spreading, or from developing in the first place, researchers report they may have found a unique approach to tackle the insidious cancer. By using monobodies, the scientists say they have found a new way to block the action of genetic mutations found in nearly one-third of all cancers, including mesothelioma.
Researchers from the University of Illinois at Chicago (UIC) report they are turning to monobodies, synthetic binding proteins, instead of antibodies, when looking at a key target of many cancers – the RAS family of proteins. They report that the NS1 monobody, that they developed, can block the activity of the RAS proteins that control cell division and can drive healthy cells to divide uncontrollably, according to a Nov. 7 press release from the UIC.
“We did not look for a drug or specifically for an inhibitor,” said John O’Bryan, associate professor of pharmacology in the UIC College of Medicine, and a member of the UIC Cancer Center and who holds an appointment at the Jesse Brown VA Medical Center in Chicago. “We used monobody technology, a type of protein-engineering technology, to identify regions of RAS that are critical for its function.”
The RAS body of proteins, which includes K-RAS, H-RAS and N-RAS, are found in close to 90 percent of pancreatic cancers and in high levels in colon cancer, lung cancer and melanoma, according to the researchers. According to some reports, mutations of the KRAS gene (Kirsten rat sarcoma viral oncogene homolog) are found in 20 to 25 percent of lung cancers. These cancers do not respond well to standard treatments and are extremely challenging to treat.
The team developed the NS1 monobody that binds to the RAS protein and acts as an inhibitor of the K-RAS and H-RAS proteins, but not the N-RAS. NS1 works by interfering with the proteins’ ability to form a molecular pair.
“These insights may help guide the development of new therapeutic approaches to treating cancer by interfering with mutant RAS function in cancer cells,” said the researchers.
Pleural mesothelioma, a rare form of cancer caused by exposure to airborne asbestos fibers, is highly aggressive and is resistant to many current treatments. Care often follows the same protocol as lung cancer, leading the mesothelioma community to keep a close eye on this research.
A Stand Up 2 Cancer dream team was funded this year to focus on KRAS-positive lung cancer. The team, led by Jeffrey Engelman, MD, PhD, Director, Thoracic Oncology & Molecular Therapeutics, Massachusetts General Hospital-Cancer Center, is focused on using existing drugs targeting mutated KRAS pathways in combination with other anti-cancer drugs to develop therapies that can kill these lung cancer cells. Visit the StandUp2Cancer website to find out more about the Dream Team.
“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 tumor growth.”
See the Nov. 7 issue of Nature Chemical Biology for the full report of the study conducted by the UIC team.