Emerging therapies in gastrointestinal cancers

Table 1 Selected ErbB-targeted monoclonal antibodies

Drug/agent	Type	Target	Company/institution	Stage of development
Trastuzumab (Herceptin)	Humanized mAb	ErbB-2	Genentech/Roche	Approved for ErbB-2 over expressing breast cancer in 1998
Cetuximab (Erbitux/IMC-225)	Human-mouse Chimeric mAb	EGFR	ImClone/Merck KGaA Bristol-Myers Squibb	Approved for colorectal cancer, Phase III trials ongoing for HNSCC and NSCLC in 2004
Panitumumab (ABX-EGF)	Fully Human mAb	EGFR	Abgenix	Phase III trials for renal cancer, prostate cancer, pancreatic cancer, colorectal and NSCLC, esophageal cancer
Pertuzumab (Omnitarg/2C4)	Humanized mAb	ErbB-2	Genentech	Phase II trials for ovarian cancer, breast cancer, prostate cancer and NSCLC
Matuzumab (EMD-72000)	Humanized mAb	EGFR	Merck KGaA	Phase II trials ongoing for gynaecological cancer, pancreatic cancer and esophageal cancer
Thera CIM (hR3)	Humanized mAb	EGFR	YM Biosciences/CIM	Phase II trials for HNSCC
HuMab-Mouse (MDX-447)	Humanized mAb	EGFR	Medarex/Merck KGaA	Preclinical trials ongoing. Phase II trials ongoing for HNSCC
Mab 806	-	EGFR(del 2-7)/ EGFR vIII	Ludwig Institute	Preclinical trials ongoing.

EGFR: Epidermal growth factor receptor; mAb: Monoclonal antibody; NSCLC: Non-small-cell lung cancer; HNSCC: Head and neck squamous-cell cancer.

Table 2 Selected ErbB-targeted small molecule inhibitors

Drug/agent	Molecular properties	Target Selectivity	Clinical activity in cancer type	Company/Institution	Stage of development
Gefitinib (ZD 1839; Iressa)	Reversible TKI	EGFR inhibitor	NSCLC, HNSCC, colorectal cancer and breast cancer	AstraZeneca	Approved for NSCLC in 2003, ongoing Phase III Trials for other cancers
Erlotinib (OSI-774; Tarceva)	Reversible TKI	EGFR inhibitor	NSCLC, HNSCC, colorectal cancer and pancreatic cancer	Genentech/ OSI pharmaceuticals	Approved for NSCLC in 2005, ongoing Phase III Trials for other cancers
Canertinib (CI-1033)/(PD183805)	Irreversible TKI	EGFR/ErbB-2 inhibitor	NSCLC, HNSCC, Ovarian cancer, breast cancer	Pfizer	Phase II
Lapatinib (GW2016)	Reversible TKI	EGFR/ErbB-2 dual inhibitor	Breast cancer	GlaxoSmithkline	Phase III
EKB-569	Irreversible TKI	EGFR inhibitor	Colorectal cancer, cancer, HNSCC, and NSCLC	Wyeth-Ayerst	Phase II
AEE788	TKI	EGFR/ErbB-2/VEGFR	Anti-proliferative effects in tumor cell lines and animal models of cancer	Novartis	Phase I
EXEL 7647/EXEL 0999	TKI	EGFR/ErbB-2/VEGFR		EXELIXIS	Phase I
PKI-166	Reversible TKI	EGFR/ErbB-2	Thyroid, Renal, colorectal, HNSCC, and NSCLC	Novartis	Phase I
PD 168393	Irreversible TKI	EGFR	-	Calbiochem	Preclinical
AG-1478	Irreversible TKI	EGFR	-	Calbiochem	Preclinical
CGP-59326A	Reversible TKI	EGFR	-	Novartis/	Preclinical
BIBX 1382	TKI	EGFR	-	Boehringer/Ingelheim	Preclinical

EGFR: epidermal growth factor receptor; TKI: tyrosine-kinase inhibitor; NSCLC: non-small-cell lung cancer; HNSCC: head and neck squamous-cell cancer, VEGFR: vasculo-endothelial growth factor receptor.