… and functions of SHP2, and briefly review the development of SHP2 inhibitors. Importantly, …
to overcome drug resistance and synergistic tumor immunotherapy using SHP2 inhibitors. We …

… , SHP2 … SHP2, during adaptive resistance to MEKis, impaired the interaction with KSR1,
activating KSR1 to promote MAPK signaling. In conclusion, SHP2 promotes adaptive resistance …

… SHP2 blockade by SHP099 in combination with sorafenib attenuated the adaptive resistance
… Our results suggest that SHP2 inhibition could be a potential strategy to override sorafenib …

… To date, eight SHP2 inhibitors have advanced into clinical trials as … adaptive resistant
cancers. In this Perspective, we briefly summarize the strategies targeting SHP2 including inhibitors…

… Here, by using two new affinity reagents that allow direct monitoring of KRAS G12C
activation and inhibition, we find that G12C-Is evoke adaptive resistance in vitro and in vivo by …

… have shown promise in overcoming resistance to kinase inhibitors … SHP2 inhibitors are
used to overcome drug resistance, especially to immunotherapy agents. Many SHP2 inhibitors …

… Allosteric SHP2 inhibitors (SHP2i) in the clinic prevent SHP2 activation, block proliferation
… cancers, and overcome “adaptive resistance.” To identify SHP2i resistance mechanisms, we …

… and inhibition, we find that G12C-Is evoke adaptive resistance in … inhibitors (48, 49, 71-75),
G12C-Is induce RTK/RTK ligand genes, increasing RTK signaling to RAS. SHP2 inhibition…

… inhibitors, SHP2 inhibitors, and MEK/ERK inhibitors were assessed in combination with KRAS
G12C inhibitors … suggest that SHP2 inhibition can abrogate adaptive feedback reactivation …

… We further investigated the role of SHP2 phosphorylation on Tyr62 … of adaptive resistance
through reactivation of the SHP2-RAS-ERK axis. Finally, we show that this adaptive resistance …