Table 1. EGFR alterations in cancer and mechanisms of resistance to EGFR TKIs.

Cancer	Predominant EGFR alteration	EGFR inhibitors	Resistance mechanisms
Non-small cell lung cancer	EGFR activating mutations	Erlotinib* Gefitinib Afatinib Dacomitinib Canertinib Neratinib CO-1686 WZ4002 Cetuximab	Secondary EGFR mutations, PI3K/AKT, MAPK, MET, AXL, HER2, NFĸB, BRCA1, BIM IGF1R, FGFR (Preclinical)
Glioma	EGFRvIII	Dacomitinib	PTEN loss
Colorectal cancer	EGFR overexpression	Cetuximab* Panitumumab*	KRAS mutations
Head and neck squamous cell carcinoma	EGFR overexpression	Cetuximab* Afatinib	Preclinical
Pancreatic cancer	EGFR and ligand upregulation	Erlotinib*	Preclinical

^* FDA approved.