More than a quarter of all cancers exist because of mutations in the RAS family of genes. Considering the pivotal role of these oncogenes, and despite intensive efforts, no effective pan-RAS therapies have successfully made it to the clinic. Notably, these efforts have mainly focused on switching off the activity of specific RAS mutants.
In our previous ERC-funded project, we discovered that a class of neuronal proteins, called SHANKs, is present in RAS-driven cancers. The SHANK3 family member binds to active/mutant RAS proteins and dampens RAS function. In our RASATaC ERC-PoC, we investigated if targeting SHANK3 could be an effective therapy in RAS-driven cancers. We developed several approaches to monitor the effect of SHANK3 loss on RAS activity and signalling. We found a significant impact on the size of RAS-driven tumours in animals when SHANK3 was lost compared to untreated tumours. Based on our data, we have now established several avenues and collaboration with industry to find drugs to target SHANK3 and to battle RAS-driven cancers.
