Targeted agents for HER2-positive MBC. Diagram depicting the molecular targets of approved and investigational agents for HER2-positive MBC. Abbreviations: Akt, protein kinase B; c-kit, stem cell factor receptor; EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; hsp90, heat shock protein 90; IGF-1R, insulin-like growth factor-1 receptor; MBC, metastatic breast cancer; mTOR, mammalian target of rapamycin; PDGFR, platelet-derived growth factor receptor; PI3K, phosphoinositide-3-kinase; RTK, receptor tyrosine kinase; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.