Regulating RAS Activity to Target RAS-Driven Cancers

ended

More than a quarter of all cancers are driven by mutations in the RAS family of genes. Considering the key role of these oncogenes, and despite intensive effort, no effective anti-RAS strategies have successfully made it to the clinic. In our ERC-CoG project, we found that a class of scaffold proteins, expressed in cancer, bind to active/mutated forms of RAS proteins to moderate RAS signalling. Accordingly, we find that loss of one of the scaffolding protein isoforms in RAS-mutant cancers triggers cytotoxic signalling, leading to cell death. As such, drugging this scaffold protein could not only i) represent a completely innovative approach to target RAS-driven cancers that exploits the oncogene’s function, but also ii) deliver the first truly effective cancer treatment for patients that do not respond to current standards of care. In this ERC-PoC, we aim to prove that therapeutic targeting of the scaffold protein is effective in vivo, and to explore the commercial avenues to exploit this finding.