Figure 2. More RAS vulnerabilities, downstream.

Insight into additional aspects of RAS protein and pathway regulation reveal more ways to potentially target RAS. Biancucci et al. showed that endopeptidase RRSP modification of RAS (I) impairs its interaction with downstream kinase RAF¹⁷. Looking further downstream still, Blake et al. applied a MYC degradation screen to identify the kinase CDK9 as a positive regulator of MYC protein stability (II) and, consequently, cell growth and survival³⁹. Some clinically approved therapeutics indicated for targeting RAS activation and signaling in cancer are noted (red).