Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts

•RAS mutations have been associated with a range of malignancies and with developmental disorders called RASopathies.•Cancers associated with sporadic and germline RAS mutations are dissimilar in histological origins and mutational subtypes.•This disparity highlights our incomplete understanding of the relationship between the RAS–MAPK pathway and cancer.•Recent advances in targeting Ras G12C, HRAS and MEK have led to renewed interest in...