… -resistant cell lines as well as patient-derived xenografts. Upon sorafenib treatment, adaptive
resistance … We found that the SHP2 inhibitor SHP099 abrogated sorafenib resistance in …

… 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 …

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

… effect of the SHP2 inhibitor on T cells in vivo, and further, the impact of SHP2 inhibition on
the … to increase sensitivity to an immune checkpoint inhibitor in checkpoint resistant tumors. …

… 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…

… of SHP2 inhibitors in 3D growth environments as compared to traditional 2D culture. In
vivo, SHP2 inhibition … with FGFR-targeted kinase inhibitors. Overall, we posit that combined …

… Next-generation SHP2 inhibitors will likely be needed to address resistance to the initial
class of allosteric SHP2 inhibitors. On-target mechanisms of drug resistance caused by site …

… inhibitor sorafenib in HCC is limited by adaptive resistance. Recent studies showed SHP2
was markedly increased in sorafenib-resistant cell … The SHP2 inhibitor SHP099 in combination …

… SHP2 but exhibit resistance to SHP2 inhibitors in vitro and in vivo. Treatment of such models
with SHP2 inhibitors … by FGFR inhibitors or high doses of SHP2 inhibitors. Mechanistically, …

… adaptive clinical resistance to KRASG12C 4 inhibitor activity, with or without augmentation by
inhibitors of SHP2… in 9 the resistance setting to KRASG12C + SHP2 inhibition that warrants …