Targeting SHP2 Signaling in Lung Cancer

SHP2 is an essential molecule in many signaling cascades. It is encoded by the PTPN11 gene, a nonreceptor protein tyrosine phosphatase, and it contains a catalytic PTP domain and two SH2 domains.1 SHP2 is recruited by different receptor tyrosine kinases (RTKs) to participate in various signaling pathways, such as the activation of the RAS-RAF-MEK-ERK pathway through mediation of signaling by EGFR,2–4 recruitment by FGFR1 to enhance PI3K/AKT signaling,5 negative regulation of the JAK/STAT pathway,3 and immunologic responses through the programmed death 1 (PD-1) pathway (Fig. 1).