Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors

Table 2

Candidate predictive markers for SCCHN response to EGFR-targeted therapies.

Tumor molecular marker	Study/ reference	Tumor type(s)	N tumors assessed	N tumors with molecular marker	Assay method	Positive scoring definition(s)	Associated with EGFR tumor levels
EGFR gene amplification	Sheu et al., 2009 [24]	OSCC	128	22 (17.2%)	FISH	>2.5 EGFR signals relative to Cen7 signal	Yes
	Ch’ng et al., 2008 [25]	SCCHN	39	18 (46%)	FISH	>2 EGFR signals relative to Cen7 signals or ≥15 EGFR copies per cell in ≥10% of cells	No
	Chiang et al., 2008 [26]	OSCC	42	14 (33%)	Q-PCR	≥2 EGFR gene copies relative to LINE1 element	No
	Temam et al., 2007 [27]	SCCHN	134	22 (17%)	Q-PCR (𝑛=134) and FISH (𝑛=16)	Q-PCR: >mean + 1.96 standard deviations of normal WBC EGFR gene copy number normalized to 𝛽-globin; FISH: ≥4 gene copies in 40% of cells or gene/chromosome ratio >2 or≥15 gene copies in ≥10% of cells	No significant correlation between EGFR gene amplification by FISH and EGFR IHC expression
	Chung et al., 2006 [28]	SCCHN	75	43 (58%)	FISH	≥4 gene copies in 40% of cells or gene/chromosome ratio >2 or ≥15 gene copies in ≥10% of cells	No
	Hanawa et al., 2006 [29]	ESCC	106	53 (50%)	FISH	EGFR signal > Cen7 signal	Yes
	Mrhalova et al., 2005 [30]	SCCHN	33	7 (21%)	FISH		No
	Koynova et al., 2005 [31]	Larynx cancers	1080	112 (10.4%)	FISH	≥4 EGFR signals relative to Cen7 in ≥10% of cells	NA
	Freier et al., 2005 [32]	SCCHN	609	12.70%	FISH	≥8 EGFR signals relative to Cen7 in ≥10% of cells	NA
KRAS mutations	Sheu et al., 2009 [24]	OSCC	29	2 (6.9%)	Sequencing	KRAS Q61H mutation	NA
	Lea et al., 2007 [33]	ORAL cancers	122	5 (4%)	GAC database analysis	Somatic missense, nonsense, silent point mutations, frameshift and in-frame deletions and insertions	NA
	Forbes et al., 2008 [34]	Oral, pharynx, larynx cancers	937	24 (3%)	COSMIC database	Datamining of published reports and somatic mutation screening from Cancer Genome Project	NA
HRAS mutations	Forbes et al., 2008 [34]	Oral, pharynx, larynx cancers	686	75 (10%)	COSMIC database	Datamining of published reports and somatic mutation screening from Cancer Genome Project	NA
	Lea et al., 2007 [33]	ORAL cancers	170	19 (11%)	GAC database analysis	Somatic missense, nonsense, silent point mutations, frameshift and in-frame deletions and insertions	NA
	Anderson et al., 1994 [35]	ORAL cancers	35	6 (22%)	PCR and restriction length polymorphism analysis	Presence of appropriately altered restriction enzyme digested DNA fragment	NA
PI3KCA mutations	Murugan et al., 2008 [36]	SCCHN	37	2 (5%)	PCR and direct sequencing exons 9 and 20	Somatic missense, nonsense, frameshift, in-frame deletions, and insertions	NA
	Fenic et al., 2007 [37]	SCCHN	33	0 (0%)	PCR and direct sequencing exons 9 and 20	Somatic missense mutations	NA
	Qiu et al., 2006 [38]	SCCHN	38	4 (11%)	PCR and direct sequencing exons 1, 4, 5, 6, 7, 9, and 20	Somatic missense mutations	NA
	Kozaki et al., 2006 [39]	OSCC	108	8 (7%)	PCR and direct sequencing exons 9 and 20	Somatic missense mutations	NA
PTEN mutations	Shin et al., 2002 [40]	OSCC	86	4 (5%)	PCR and exon direct sequencing	Somatic missense, nonsense, silent point mutations, frameshift, in-frame deletions, and insertions	NA
	Poetsch et al., 2002 [41]	SCCHN	52	7 (13%)	PCR and exon direct sequencing	Somatic missense, nonsense, frameshift, in-frame deletions, and insertions	NA
	Mavros et al., 2002 [42]	OSCC	50	0 (0%)	PCR and exon direct sequencing	Somatic missense, nonsense, frameshift, in-frame deletions, and insertions	NA
	Shao et al., 1998 [43]	SCCHN	19	3 (16%)	PCR and exon direct sequencing	Somatic missense, nonsense, frameshift, in-frame deletions, and insertions	NA

Squamous cell carcinoma of the head and neck (SCCHN), oral squamous cell carcinoma (OSCC), esophageal squamous cell carcinoma (ESCC), fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (PCR), centromere 7 (Cen7), Genetic Alterations in Cancer (GAC) database, and the Catalogue of Somatic Mutations in Cancer (COSMIC) database.