However, given SHOC2 repression did not lead to a sustained treatment response likely due to both compensatory upstream activation of RTK/Ras signaling and tumor heterogeneity within non-MES cells not dependent on Ras signaling, synergistic combinations targeting the parallel susceptibilities of non-MES cells will also be critical, and it will be important to define whether CDK4/6 inhibitors targeting CDKN2A/B loss may be useful in this context. The gene discussed is SHOC2; the disease is neoplasm.