Figure 2.

Mechanism of resistance to MET target therapies. (A) the on-target resistance mutations. These mutations impacted the Juxtamembrane domain (RED) and the Tyrosine kinase domain (orange). The multi-docking site (brown) without evidence of resistance mutations. (B) Canonical MET signaling pathways acquire resistance mutations such as STAT, PI3K, and KRAS amplification (amp), AKT, mTOR signaling overexpression (arrow up), KRAS mutations, and crosstalk’s mediate PI3Kamp and GSK3b inhibition, Axin downregulation (down arrow) followed by overactivation of b-catenin signaling. (C) The acquired resistance mutations impact the MET parallel receptor tyrosine kinase signaling after using MET-TKI. Therefore, the colors of the target drugs (MET inhibitors) are related to the color of mutations.