Table 3.

Efficacy of BI 853520 and expression of E-cadherin and hsa-miR-200c-3p in human adenocarcinoma models

Organ derivation	Cell line	Median TGI (%)	Sensitivity	E-cadherin protein expression	CDH1 mRNA expression (log 2)	hsa-miR-200c-3p expression (log 2)
Colon/rectum	LoVo	14 (n.s.)	Resistant	Positive	8.80	13.69
	SW480	26 (n.s.)	Resistant	Low	6.63	13.67
Kidney	A-498	93	Highly sensitive	Negative	4.19	8.25
	Caki-1	66	Moderately sensitive	Negative	5.69	n.a.
Lung	Calu-6	102	Highly sensitive	Negative	4.06	7.25
	HCC-461	102	Highly sensitive	Negative	4.49	6.38
	NCI-H2122	45 (n.s.)	Resistant	Negativea	8.33	13.56
	A549	15 (n.s.)	Resistant	Positive	9.07	n.a.
Ovary	A2780	89	Highly sensitive	Negative	4.11	n.a.
	SK-OV-3	57	Moderately sensitive	Positive	6.97	10.25
	TOV-21G	93	Highly sensitive	Negative	4.70	7.63
Pancreas	AsPC-1	13 (n.s.)	Resistant	Positive	9.02	13.28
	MIA PaCa-2	104	Highly sensitive	Negative	3.76	7.90
	PANC-1	83	Moderately sensitive	Low	5.56	7.06
Prostate	PC-3	93	Highly sensitive	Low	8.87	6.24
Stomach	Hs 746T	72	Moderately sensitive	Negative	4.04	9.89

Mice bearing subcutaneous tumors were treated with 50 mg/kg BI 853520 once daily per os (seven or ten animals per group). E-cadherin protein expression in control tumors was determined by immunohistochemistry; tumors were classified as “negative” if expression was not detectable, as “low” if less than 30% of cells expressed E-cadherin on their membranes, and as “positive” if 30% or more expressed E-cadherin. Expression of CDH1 (=gene encoding E-cadherin) mRNA and of hsa-miR-200c-3p microRNA was analyzed using Affymetrix GeneChip Exon 1.0 and Affymetrix GeneChip miRNA 3.0, respectively (2–3 tumors per group)

n.s. statistically not significant (p > 0.05), n.a. data not available

^aCDH1 mutation in NCI-H2122