… Next, we used individual RTK inhibitors to demonstrate that SHP2-dependent pathway
reactivation is due to RTK activity and to identify which RTKs were responsible in KRAS-mutant …

… SHP2 inhibition acts upstream of RAS to abrogate MEKi–evoked ERK MAPK pathway
reactivation. A and B, Immunoblots of whole-cell lysates or GST-RBD–precipitated (RAS-GTP, …

… SHP2 is an activator of the RAS pathway, and we and others have shown that pharmacologic
inhibition of SHP2 … Here we report inhibition of growth and downstream RAS–MAPK …

… by reactivation of RAS-MEK-ERK and AKT pathways. Combined use of SHP2 inhibitor (10)
with sorafenib can block the reactivation of MEK/ERK and AKT signaling pathways, thus …

… multiple RTK upon mTOR inhibition in HCC which, through SHP2, leads to reactivation of
the mTOR pathway. We show that co-inhibition of both mTOR and SHP2 is highly synergistic in …

… Thus, our results suggest that SHP2 inhibition can mitigate … feedback reactivation of RAS
and MAPK pathway signaling in … SHP2 inhibition can abrogate adaptive feedback reactivation …

… pathway inhibition by SHP2 inhibitors may promote the open conformation of SHP2 and
lead to resistance to SHP2 inhibitors. … this RAS reactivation following initial SHP2 inhibition is …

… of MEK induces negative feedback to increase the RTK activity that leads to the reactivation
of RAS/Raf/ERK pathway or increases the activities of other cascades, such as PI3K/AKT …

… -site inhibitors generally showed off-target inhibition of other … , allosteric SHP2 inhibitors
with striking inhibitory potency … Reactivation of RAS pathway signaling may underlie the lack …

… cancers, among others, through blocking signal transduction from most RTK that are
reactivated through loss of negative feedback following ERK pathway inhibition [19,24,26,29-38]. …