Tyrosine kinase inhibitors (TKIs) are drugs that inhibit the phosphorylation, and subsequent activation, of tyrosine kinases. TKIs are typically used as cancer therapeutics, but development of resistance to TKIs in cancers is common. This pathway describes several mechanisms of TKI resistance in the context of EGFR signaling. Epidermal Growth Factor Receptor, EGFR, is a transmembrane tyrosine kinase that binds to the EGF-family of ligands. It activates several downstream signaling cascades, including MAPK, and leads to DNA synthesis and cell proliferation. Mutations and over-expression in EGFR is implicated in many cancers.
The section of the pathway outlined in pink corresponds to mechanisms of TKI resistance.
This pathway was based on [KEGG](https://www.kegg.jp/kegg-bin/show_pathway?hsa01521). Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.