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. Author manuscript; available in PMC: 2014 Jun 9.

Published in final edited form as: Nat Med. 2013 Nov 7;19(11):1389–1400. doi: 10.1038/nm.3388

Table 2.

Overview of EGFR resistance mechanisms

	Lung (EGFR TKIs)	Colon (EGFR mAbs)	Head and neck (cetuximab)
Primary resistance	EGFR exon 20 insertion⁷,^a BIM deletion³²,^a EGFR T790M^41,179	KRAS^47,48,^a PIK3CA exon 20 (refs. 47,48)^a BRAF mutation^47,48,^a PTEN deletion^47,48,^a
Acquired resistance
EGFR modification	T790M⁸²,^a	S492R⁴²,^a	EGFRvIII¹⁸¹
Alternative pathway activation	BRAF⁵¹,^a CRKL⁶⁵ DAPK¹⁸² FGF^69–71 HER2 (ref. 45)^a HER3 (ref. 68) IGF^183,184 JAK2 (ref. 72) MED12 (ref. 185) MET⁴⁴,^a NF-κB¹⁸⁶,^a PTEN loss^63,64 PUMA¹¹⁴ ROR1 (ref. 113) VEGF¹⁸⁷	HER2 (ref. 46)^a IGF¹⁸⁹,^a KRAS^49,50,^a MET¹⁹⁰	Aurora¹⁹¹ HER2 HER3 MET¹⁹²
Histologic transformation	Acquisition of stem cell properties⁷³ EMT (AXL, Notch-1 or TGF-β activation)^57–60,185,^a Small cell lung cancer transformation¹⁸⁸,^a		EMT^193,194

^a

Mechanisms have also been identified in patient tumors.