SHP2 is a nonreceptor tyrosine kinase phosphatase that acts as an upstream positive regulator of the RAS-MAPK pathway,243 along with modulating other tumor-related pathways and immune cell signaling.207,244–246 It thus plays a pivotal role in tumorigenesis, as proven in several models of KRAS-mutant NSCLC.116,247 Accordingly, many SHP2 inhibitors have undergone preclinical development, showing single-agent activity against the cycling of KRASG12C mutants via the inhibition of GDP-GTP exchange,207,244 and some have entered the clinical trial arena. The gene discussed is KRAS; the disease is non-small cell lung carcinoma.