Targeting the insulin-like growth factor pathway in hepatocellular carcinoma

Table 1 Agents targeting insulin-like growth factor system

Compound	Company	Description	Target	Treatment	Status	Ref./Clinical trial	Unaffected mitogenic IGF proteins/metabolic signaling status
Octreotide	Novartis Farmaceuticals	Somatostatin homologue	IGF-I	Monotherapy	Preclinical	[200,201]	IGF-II and insulin interaction with IGF-IR, IR-A, IR-B/IR-A and HRs/not affected
DX-2647		Neutralizing antibody	IGF-II and proIGF-II	Monotherapy	Preclinical	[202]	Insulin interaction with IR-A, IR-B/IR-A and HR-A/not affected
MEDI-573	AstraZeneca (MedInmune)	Neutralizing antibody	IGF-II and IGF-I	MEDI-573 + Sorafenib	Phase I	NCT01498952; [192,203]
Cixutumumab (IMC-A12)	ImClone Systems Inc	Blocking antibody	IGF-1R	Monotherapy	Phase II	NCT00639509; [53,215,216]	IGF-I, IGF-II and insulin interaction with IR-A, IR-B/IR-A and HRs/not affected
				Cixutumumab + Sorafenib	Phase I	NCT01008566; NCT00906373
AVE1642	Sanofi-Aventis	Blocking antibody	IGF-1R	Monotherapy	Phase I	NCT00791544; [125]
				AVE-1642 + Sorafenib	Phase II	NCT00791544
				AVE-1642 + Erlotinib	Phase II	NCT00791544
BIIB022	Biogen-Idec	Blocking antibody	IGF-1R	BIIB022 + Sorafenib	Phase I	NCT00956436; [53,223]
Figitumumab (CP-751,871)	Pfizer	Blocking antibody	IGF-1R, HRs	Monotherapy	Preclinical	[224,225]	IGF-II and insulin interaction with IR-A, IR-B/IR-A/not affected
Linsitinib (OSI-906)	OSI Pharmaceuticals	TKI	IGF-1R, IR	Monotherapy	Phase II	NCT01101906; [226,227]	/impaired.
				OSI-906 + Sorafenib	Phase II	NCT01334710
AG1024 (Tyrphostin)		TKI	IGF-1R, IR	Monotherapy	Preclinical	[231]
NVP-AEW541	Novartis Farmaceuticals	TKI	IGF-1R, IR	Monotherapy	Preclinical	[232,233]
BMS-536924	Bristol-Myers Squibb	TKI	IGF-1R, IR	Monotherapy	Preclinical	[234]
GSK1904529A	GlaxoSmithKline	TKI	IGF-1R, IR	Monotherapy	Preclinical	[235]

IGF: Insulin-like growth factor; IGF-IR: IGF-I receptor; IR: Insulin receptor; TKI: Tyrosine kinase inhibitor.