Table 4.

Therapy resistant ALK alterations

Drug (type)	Resistant variant(s)	Tumor type	Level of evidencea	Reference(s)
Crizotinib (ALK TKI)	Amplification-EML4-ALK	NSCLC	3A	Doebele et al. 2012b
	1151insT L1152R C1156Y F1174V G1202R S1206Y G1269A	NSCLC	3A	Choi et al. 2010; Doebele et al. 2012b; Katayama et al. 2012; Ou et al. 2015; Zou et al. 2015
	EML4-ALK/1151insT EML4-ALK/L1152R EML4-ALK/C1156Y EML4-ALK/L1196M EML4-ALK/L1198P EML4-ALK/D1203N		3B	Choi et al. 2010; Doebele et al. 2012b; Katayama et al. 2012; Ou et al. 2015; Zou et al. 2015
	NPM1-ALK	ALCL	3B	Ceccon et al. 2013
	RANBP2-ALK	IMT	3A	Sasaki et al. 2010
Ceritinib (ALK TKI)	EML4-ALK/1151Tins EML4-ALK/L1152R EML4-ALK/C1156Y EML4-ALK/F1174C EML4-ALK/G1202R		3B	Friboulet et al. 2014
Alectinib (ALK TKI)	EML4-ALK/I1171Tins EML4-ALK/V1180L EML4-ALK/G1202R	NSCLC	3B	Katayama et al. 2014; Kodama et al. 2014

Only clinically available drugs are listed in the table.

TKI, tyrosine kinase inhibitor; NSCLC, non-small-cell lung cancer; NB, neuroblastoma; ALCL, anaplastic large-cell lymphoma; IMT, inflammatory myofibroblastic tumor; CRC, colorectal cancer.

^aDefinition of level of evidence based on Meric-Bernstam et al. 2015.