Molecular Aspects of Breast Cancer Metastasis to the Brain

Table 2

Current targeted therapies and their use in metastatic breast cancer (MBC).

Drug	Class	Targets	Clinical indications	Reference
Trastuzumab	mAb	HER2	Single agent for HER2+ MBC; used in combination with paclitaxel as first-line therapy for HER2+ MBC	[58]
Lapatinib	TKI	HER1/2	Active in Trastuzumab-resistant, HER2+ breast cancer; crosses the BBB and suppresses CNS metastasis used in combination with Capecitabine for HER2+ MBC	[41]
Pertuzumab	mAb	HER2	Impairs HER2 homo-/hetero-dimerisation; active in Trastuzumab-resistant HER2+ breast cancers; not currently approved for MBC	[59]
Neratinib	TKI	HER1/2	Inhibits HER2 autophosphorylation and suppresses downstream signalling; active in HER2+ patients with and without Trastuzumab pretreatment; not currently approved for MBC	[60]
Bevacizumab	mAb	VEGF	Antiangiogenic therapy for MBC in combination with Docetaxel or Paclitaxel for first-line treatment	[61]
Sorafenib	TKI	VEGFR; PDGFR; Raf	Multitarget receptor tyrosine kinase inhibitor; FDA-approved for advanced renal cancer and hepatocellular carcinoma	[62]
Axitinib	TKI	VEGFR; PDGFR	Currently in phase III clinical trial for metastatic renal cell carcinoma	[63]
Sunitinib	TKI	VEGFR; PDGFR; KIT	Antiangiogenic therapy; FDA-approved for renal cell carcinoma and Gleevec-resistant gastrointestinal stromal tumours; effective as a single agent for metastatic breast cancer (phase II study)	[64–66]
Pazopanib	TKI	VEGFR; PDGFR; KIT	Anti-angiogenic therapy; FDA-approved for renal cell carcinoma; combination with Lapatinib has superior activity as the first-line treatment for MBC (phase II study)	[67]

Abbreviations: BBB: blood-brain barrier; CNS: central nervous system; HER1: Epidermal Growth Factor Receptor (EGFR); mAb: monoclonal antibody; KIT: Mast/stem cell growth factor receptor gene; PDGFR: platelet-derived growth factor receptor; TKI: tyrosine kinase inhibitor; VEGFR: vascular endothelial growth factor receptor.