Anti-EGFR treatment resistance in patients with wild-type RAS metastatic colorectal cancer: Three case reports

Table 1 Clinical characteristics, anti-EGFR therapy responses, and interventions in 3 cases of metastatic colorectal cancer

	Case 1	Case 2	Case 3
Clinical baseline
Age	58	48	68
Gender	Male	Male	Male
Primary tumor location	Left-sided colon	Right-sided colon	Rectal
Metastatic site	Liver	Liver	Liver
Anti-EGFR therapy regimen	Cetuximab + mFOLFOX6	Cetuximab + FOLFIRI	Cetuximab + FOLFOX
Cycle of resistance onset	17	7-8	1-2
Summary of resistance mechanism	Acquired resistance	Acquired resistance	Primary resistance
KRAS/NRAS/BRAF/PIK3CA status	KRAS exon 2 mt	-	KRAS exon 2 mt
HER2 expression/amplification	-	+++	-
Clinical interventions	Palliative resection of the primary lesion, followed by resection of the hepatic metastatic lesion 12 months later	Palliative primary tumor resection was performed to resolve intestinal obstruction	Radical resection of sigmoid colon cancer, followed by resection of the hepatic metastatic lesion 14 months later

mt: Mutation.

Table 2 Summary of literature on acquired resistance to anti-EGFR therapy

Resistance mechanism	Detection source	Number of cases (%)	Ref.
KRAS gene mutation	Tissue	1/10 (10)	Montagut et al[5]
	Serum	9/24 (37.5)	Diaz et al[6]
	Tissue and Serum	5/11 (45.5)	Misale et al[7]
	Tissue and Serum	3/7 (42.9)	Bardelli et al[8]
	Serum	22/24 (91.7)	Bettegowda et al[9]
	Serum	3/4 (75)	Misale et al[10]
NRAS gene mutation	Serum	9/24 (37.5)	Bettegowda et al[9]
	Serum	2/4 (50)	Misale et al[10]
EGFR gene mutation	Tissue	2/10 (20)	Montagut et al[5]
	Serum	2/24 (8.3)	Bettegowda et al[9]
KRAS gene amplification	Tissue and Serum	1/11 (9.1)	Misale et al[7]
	Serum	4/10 (40)	Mohan et al[11]
HER-2 gene amplification	Tissue	2/2 (100)	Yonesaka et al[12]
MET gene amplification	Tissue and Serum	3/7 (42.9)	Bardelli et al[8]
	Serum	1/10 (10)	Mohan et al[11]