ReviewGene-to-screenRecent advances in cancer drug discovery targeting RAS

•Recent reports on RAS have shared new information on structure and binding pockets.•Efforts to target the KRAS G12C mutation specifically have shown promising results.•Other approaches have targeted various protein complexes.•These advances could lead to development of new effective cancer drugs targeting RAS.

Mutated RAS is present in 30% of human tumors, appearing in 90% of pancreatic, 45% of colon and 35% of lung cancers. These high occurrences make RAS one of the most important drug targets in oncology. Three decades of effort to target RAS have been unsuccessful in generating drug therapies suggesting that it might represent an 'undruggable' target. However, recent reports highlighting new approaches for targeting RAS have uncovered more information on protein structure and identified new binding pockets. Efforts to target the KRAS G12C mutation specifically have shown promising results whereas other approaches have targeted various protein complexes. These advances could lead to development of new effective cancer drugs targeting RAS.