CRUK, NCI fund Ras inhibitor tests, create commercial path

Beatson Institute for Cancer Research, Glasgow (Vojtěch Dostál CC BY-SA 4.0)

Cancer Research UK (CRUK) has teamed up with the National Cancer Institute (NCI) to fund work on inhibitors of Ras proteins. The partners want to develop tests to analyze Ras inhibitors and have brought Sixth Element Capital-managed CRT Pioneer Fund (CPF) on board to push resulting assets into commercial development.

CRUK and CPF are putting up £2.5 million ($3.2 million) to bankroll a transatlantic collaboration. The initiative brings together researchers at a CRUK drug discovery center in Glasgow, Scotland, and a team based out of NCI’s facilities in Frederick, Maryland. Together, the two groups hope to add impetus to long-running efforts to drug Ras by developing tests to analyze inhibitors of the cancer target.

Years of unsuccessful research programs have given Ras a reputation for being “undruggable.” When researchers sought to stop Ras farnesylation, they found a backup system that rendered their efforts futile. And when they then went after the downstream effector Raf kinase, they learned inhibitors actually activated the pathway.

Despite these and other setbacks, researchers remain drawn to Ras. Mutations of the different types of Ras gene are found in 20% or more of patients with seven types of cancer, including tumors affecting the pancreas, lung and skin. This, coupled with the poor outcomes of patients with cancers driven by Ras genes, has sustained interest in the target in the face of setbacks and a lack of understanding about the associated biology and biochemistry.

NCI is trying to fill in these knowledge gaps and advance the field through its RAS Initiative. And, in CRUK, it has found a partner that buys into its vision of a global research network and belief that advances in protein analysis and ideas of how to block of Ras function will make it possible to hit the target.

“Our team is determined to challenge the dogma that Ras is ‘undruggable.’ This collaboration is our biggest yet and will double our resource targeting Ras,” Martin Drysdale, who heads up CRUK’s Glasgow drug discovery site, said in a statement. “Instead of scientists working and thinking in isolation, the NCI has created a research hub to pull together all the best science and expertise.”

CPF will handle the commercial prospects of compounds arising from the collaboration. The fund is a £50 million joint venture set up by the CRUK’s tech transfer offshoot Cancer Research Technology and the European Investment Fund. Sixth Element Capital manages the fund with a remit to invest directly in oncology projects—rather than company spinouts or infrastructure—and put two-thirds of its cash into programs sourced from CRUK.