SHP2

Notes

original target text: SHP2 inhibitor

SHP2 is an enzyme called a protein tyrosine phosphatase, encoded by the gene PTPN11. Unlike most phosphatases, which dampen signaling, SHP2 acts as a positive relay in the RAS–MAPK pathway, a chain of molecular signals that many growth-factor receptors use to instruct cells to divide and survive. When growth factor receptors on the cell surface are activated, SHP2 helps transmit that signal onward to RAS and then to downstream kinases that drive proliferation. In many cancers, this pathway is hyperactive because of mutations in receptors, RAS itself, or related genes, and SHP2 sits at a convergence point that many of these mutant proteins still depend on. Blocking SHP2 with a small molecule can therefore dampen signaling driven by a broad range of upstream mutations, including some that are otherwise difficult to target directly. SHP2 inhibition is also of interest for overcoming resistance that tumors develop against other RAS-MAPK pathway drugs, since reactivation of this pathway is a common escape route. Because SHP2 also participates in normal development and immune cell signaling, its inhibition is being studied primarily in oncology, where the goal is to interrupt abnormal growth signals while managing effects on normal tissues that also rely on this pathway.