Table 1. Major causes of resistance to reversible oral EGFR-TKIs.

Primary resistance	Secondary resistance
KRAS mutation	T790 mutation
Mutations involving exon-20	MET amplication
PTEN downregulation	HER3 activation
Other mutations mutually exclusive to EGFR	HGF overexpression

KRAS, kirsten rat sarcoma oncogene; PTEN, phosphatase and tensin homolog; EGFR, epidermal growth factor receptor; MET, hepatocyte growth factor receptor; HER3, human epidermal receptor 3; HGF, hepatocyte growth factor.