… To date, eight SHP2 inhibitors have advanced into clinical … - and pathway-dependent
combination strategies of SHP2 for … ERK1/2 and Ras reactivation. These findings highlight …

… pathways can be suppressed by SHP2. Suppression and inhibition of the STAT3 activity
pathway by SHP2 … in resistance to SHP2 inhibition in vitro and in vivo by MAPK reactivation (123)…

… , MEKi in combination with an SHP2 inhibitor markedly suppressed the reactivation of the
MEK/ERK pathway; thus, the addition of the SHP2 inhibitor significantly improved the antitumor …

… binds and dephosphorylates RAS to promote re-association with RAF and re-activation of
… that RAS-MAPK pathway inactivation through SHP2 inhibition will decrease cell growth and …

… by preventing MAPK pathway reactivation from adaptive activation of other RTKs and
eliminating a subset of EGFRi-tolerant cells where RTK drives MAPK pathway reactivation (49), …

… SHP2-mediated inhibition of multiple signaling pathways … inhibition of ALK and SHP2 halts
the growth of ALK inhibitors-… preventing compensatory RAS and ERK1/2 reactivation [61]. …

… It is possible that treatment of cancers with a SHP2 inhibitor alone could prevent pathway
feedback reactivation of the MAPK pathway or block RTK-bypass mechanisms where …

… pathways. We also explore possible combinatorial approaches, wherein SHP2 inhibitors are
… reactivating the STAT signaling pathway [14,54]. As a negative effect, the overexpression of …

… These findings provide a paradigm for the design of a rational combination approach that
inhibits inhibitor-induced pathway reactivation and can be explored as a combinatorial …

… pathway. To validate that SHP099 resistance was caused by RAS-ERK pathway reactivation,
… that FLT3 was the RTK responsible for SHP2 reactivation. In support of this, we found that …