EGFR and hepatocellular carcinoma: High GABBR2 activates ERK phosphorylation, significantly preventing erlotinib-induced apoptosis.411 Moreover, in HCC, hypermethylation of the CPG island at the ADAMTS-like 5 (ADAMTSL5) locus results in its overexpression, but reduced expression and/or phosphorylation of several RTKs (MET, EGFR, PDGFRβ, IGF1Rβ, and FGFR4) and increased sensitivity to sorafenib, lenvatinib, and regorafenib were witnessed when low the ADAMTSL5 level,412 suggesting that ADAMTSL5 may contribute to TKI resistance through regulating several RTKs activity.