Table 3.

Current anti-RTK therapy of breast cancer

Molecule	Type	Target	Phase of study	Mechanism
Trastuzumab	Humanized mAb	HER	In clinical use	Inhibits HFR2 and HER3 dimerization, induces ADCC
Cetuximab	Chimeric mAb	EGFR	Phase I, II	Induces NK cell mediated ADCC
Panitumumab	Humanized mAb	EGFR	Phase II	Enhances sensitivity to DNA-damaging agents in TNBC
Nimotuzumab	Humanized mAb	EGFR	Phase I	Induces NK cell mediated ADCC
Necitumumab	Humanized mAb	EGFR	Phase II	Inhibits downstream targets in EGFR pathway, induces ADCC
Gefitinib	Reversible TKI	EGFR	Phase I, II	Reverses TAM resistance by up-regulating the ERα
Erlotinib	Reversible TKI	EGFR	Phase I, II	Suppresses CDK2 activity
Lapatinib	Reversible TKI	EGFR, HER2	In clinical use	Used as an alternate therapy in HER2 positive breast cancer
Afatinib	Irreversible TKI	EGFR, HER2	Phase II	Inhibits EGFR and HER2 signaling irreversibly
Varlitinib	Reversible TKI	EGFR, HER2, ErbB4	Phase II	Inhibits HER/MAPK signaling in TNBC
Dacomitinib	Irreversible TKI	EGFR, HER2, ErbB4	Phase I, Solid tumors	Inhibits HER2, EGFR, HER4, Akt and ERK phosphorylation
Sapitinib	Reversible TKI	EGFR, HER2, ErbB3	Phase I, Solid tumors	Showed higher inhibitory potential in tamoxifen resistant breast cancer
Vandetanib	TKI	EGFR, VEGFR2-3, RET	Phase I, II	Targets angiogenesis by inhibiting VEGFR2 and 3 signaling along with EGFR pathway
Neratinob	Irreversible TKI	EGFR, HER2, ErbB4	Phase I, II, III	Irreversibly blocks EGFR and HER2 pathway
BMS-690514	Irreversible TKI	EGFR, HER2, ErbB4, VEGFR1-3	Phase I, Solid tumors	Irreversibly blocks EGFR and HER2 pathway
AEE788	Reversible TKI	EGFR, ErbB2, VEGFR	Phase I	Targets angiogenesis by inhibiting VEGFR2 and 3 signaling along with EGFR pathway
Lucitanib	TKI	FGFR1-2, PDGFRα/β, VEGFR1-3	Phase II	Show anti-angiogenic and anti-tumoral activity by targeting FGFR and VEGFR