The product of the HER-2/neu proto-oncogene, HER2, is the second member of the 
human epidermal growth factor receptor (HER) family of tyrosine kinase receptors 
and has been suggested to be a ligand orphan receptor. Ligand-dependent 
heterodimerization between HER2 and another HER family member, HER1, HER3 or 
HER4, activates the HER2 signaling pathway. The intracellular signaling pathway 
of HER2 is thought to involve ras-MAPK, MAPK-independent S6 kinase and 
phospholipase C-gamma signaling pathways. However, the biological consequences 
of the activation of these pathways are not yet completely known. Amplification 
of the HER2 gene and overexpression of the HER2 protein induces cell 
transformation and has been demonstrated in 10% to 40% of human breast cancer. 
HER2 overexpression has been suggested to associate with tumor aggressiveness, 
prognosis and responsiveness to hormonal and cytotoxic agents in breast cancer 
patients. These findings indicate that HER2 is an appropriate target for 
tumor-specific therapies. A number of approaches have been investigated: (1) a 
humanized monoclonal antibody against HER2, rhuMAbHER2 (trastuzumab), which is 
already approved for clinical use in the treatment of patients with metastatic 
breast cancer; (2) tyrosine kinase inhibitors, such as emodin, which block HER2 
phosphorylation and its intracellullar signaling; (3) active immunotherapy, such 
as vaccination; and (4) heat shock protein (Hsp) 90-associated signal 
inhibitors, such as radicicol derivatives, which induce degradation of tyrosine 
kinase receptors, such as HER2.