Spotlight on Accessory Proteins: RTK-RAS-MAPK Modulators as New Therapeutic Targets.

The RTK-RAS-MAPK axis is one of the most extensively studied signaling cascades and is related to the development of both cancers and RASopathies. In the last 30 years, many ideas and approaches have emerged for directly targeting constituent members of this cascade, predominantly in the context of cancer treatment. These approaches are still insufficient due to undesirable drug toxicity, resistance, and low efficacy. Significant advances have been made in understanding the spatiotemporal features of the constituent members of the RTK-RAS-MAPK axis, which are linked and modulated by many accessory proteins. Given that the majority of such modulators are now emerging as attractive therapeutic targets, a very small number of accessory inhibitors have yet to be discovered.