Matthew Holderfield

FREDERICK, Md. -- An international collaboration has formed to begin an ambitious program of drug development and testing aimed at treating pancreatic cancers, lung cancers, and other malignancies driven by one of the most common and drug-resistant cancer genes.

Armed with new scientific understanding and the latest technologies, scientists at the Frederick National Lab and Cancer Research UK Beatson Institute in Glasgow, Scotland, will focus on one of the most intractable problems in cancer research — malignancies driven by mutations in RAS genes.

RAS mutations underlie 30 percent of all cancers — including colon and lung cancers — and 95 percent of pancreatic cancers, which are especially difficult to treat. Proteins made by RAS genes help control cell growth and proliferation. When mutated, they allow uncontrolled cell growth and tumor formation. The role of mutant RAS proteins has been well-known for decades, but all attempts to develop effective drugs against them have failed.

The collaboration falls under the umbrella of the National Cancer Institute’s RAS Initiative, established in 2013 to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers. The initiative is headquartered at the Frederick National Lab, which serves as a hub for engaging academic, commercial, and nonprofit researchers across the United States and overseas in a united effort.

Under a contractor Cooperative Research and Development Agreement, Frederick National Lab scientists will collaborate with scientists at Beatson's Drug Discovery Unit to develop gold-standard tests to analyze candidate drugs against RAS. The CRT Pioneer Fund, managed by Sixth Element Capital, will pursue commercial applications that may result from the collaboration.

“This is a great opportunity for the RAS program to partner with the Beatson Institute to develop promising drug leads,” said Matthew Holderfield, Ph.D., Frederick National Lab’s principal investigator on the collaboration. “Frederick National Laboratory has cultivated a depth of expertise in RAS biochemistry and cell biology, and the scientists at the Beatson Institute have made impressive advances in RAS drug discovery. It’s an excellent match of expertise at a very exciting time in the field.”

Frank McCormick, Ph.D., who is leading the RAS Initiative as a consultant to the national lab, said the effort has made progress in understanding how RAS proteins function at the molecular level and how they form signaling complexes in cell membranes.

"New technologies and tools mean we can now analyze these proteins in ways that were not possible a few years ago, and can now test new ways of blocking RAS function,” McCormick said.

Martin Drysdale, Ph.D., head of Beatson's Drug Discovery Unit, said his team is up to the challenge of finding a drug to treat RAS-driven cancers.

“This collaboration is our biggest yet and will double our resource targeting RAS,” he said. “We are excited to be joining forces with the NCI in its pioneering RAS Initiative.”

By Frank Blanchard, staff writer. Photo: Matthew Holderfield portrait by Richard Frederickson, staff photographer.