EGFR^vIII: An Oncogene with Ambiguous Role

Table 1

Agents acting specifically on EGFR^vIII or on both EGFR^vIII and EGFR^WT, based on the analysis of different cancer types.

		Specificity	Examined cancers	Activity	Stage of research	References
Agents acting only on EGFR^vIII
Immunotherapy
ADC	AMG-595	EGFR^vIII	Glioblastoma	Potentially active	Phase I	[51]
CARs	CAR-T	e.g., EGFR^vIII	Glioblastoma	Potentially active	Phase I	[52, 53]
			Lung cancer	Potentially active	Preclinical	[54]
BiTE	bscEGFR^vIII × CD3	e.g., EGFR^vIII	Glioma	Potentially active	Phase I	[55, 56, 57]
Vaccine	Rindopepimut	EGFR^vIII	Glioblastoma	Inactive	Phase III	[58]
RNA interference
Ribozymes		e.g., EGFR^vIII	Breast cancer	Potentially active	Preclinical	[59]
			Glioblastoma	Potentially active		[60]
Antisense oligonucleotides		e.g., EGFR^vIII	Glioblastoma	Potentially active	Preclinical	[61, 62]
siRNA		e.g., EGFR^vIII	Glioblastoma	Potentially active	Preclinical	[61, 63]
Agents acting on EGFR^vIIIand EGFR^WT
Tyrosine kinase inhibitors
First generation	Gefitinib	EGFR/HER1	High-grade gliomas	Limited activity	Phase II	[64, 65]
			Non-small-cell lung cancer	Active	Clinical use	[66, 67]
			Salivary gland cancer	Potentially active	Phase II	[68]
			Breast cancer	Potentially active	Phase II	[69]
			Ovarian, peritoneal, or fallopian tube cancer	Potentially active	Phase I/II	[70]
			Liver cancer	Potentially active	Phase II	[71]
	Lapatinib	EGFR/HER1/HER2	Glioblastoma	Inactive	Phase I/II	[72, 73]
			Breast cancer	Active	Clinical use	[74]
			Gastric cancer	Limited activity	Phase II	[75]
			Colorectal cancer	Potentially active	Phase II	[76]
	Erlotinib	EGFR/HER1	Gliomas	Limited activity	Phase II	[77, 78]
			Vulvar cancer	Potentially active	Phase II	[79]
			Non–small-cell lung cancer	Active	Clinical use	[80, 81]
			Pancreatic cancer	Active	Clinical use	[82]
			Head and neck cancer	Limited activity	Phase II	[83, 84]
Second generation	Afatinib	EGFR/HER1/HER2/HER4	Non-small-cell lung cancer	Active	Clinical use	[85]
			Squamous cell carcinoma of the lung	Active	Clinical use	[85]
			Head and neck cancer	Potentially active	Phase III	[86]
			Glioblastoma	Limited activity	Phase I/II	[87, 88]
			Breast cancer	Potentially active	Phase II	[89]
			Colorectal cancer	Potentially active	Phase II	[90]
Immunotherapy
Antibodies	Cetuximab	EGFR/HER1/HER2	Head and neck cancer	Active	Clinical use	[91]
			Glioblastoma	Potentially active	Phase II	[92, 93, 94]
			Colorectal cancer	Active	Clinical use	[95]
			Esophageal and gastric cancer	Limited activity	Phase II	[96]
			Non-small-cell lung cancer	Potentially active	Phase II	[97]
			Breast cancer	Limited activity	Phase II	[98]
			Prostate cancer	Inactive	Phase II	[99]
			Cervical cancer	Inactive	Phase II	[100]
	Panitumumab	EGFR/HER1	Colorectal cancer	Active	Clinical use	[101, 102]
			Biliary tract cancer	Potentially active	Phase II	[103]
			Head and neck cancer	Inactive	Phase II	[104, 105]
			Glioblastoma	Potentially active	Phase II	[106, 107]
			Breast cancer	Potentially active	Phase II	[108]
	Nimotuzumab	EGFR/HER1	Glioblastoma	Orphan status in Europe and USA	Clinical use	[109, 110]
			Head and neck cancer	Active	Phase II	[111, 112]
			Pancreatic cancer	Orphan status in Europe	Clinical use	[110, 113]
ADC	ABT-414	EGFR/EGFR^vIII	Glioblastoma	Limited activity	Phase I	[114, 115]
			Breast cancer	Limited activity	Phase I/II	[116]