Herceptin: From the Bench to the Clinic

Polypeptide growth factors play important roles in both normal and pathological development of the breast. Such growth factors promote cell proliferation, motility, and invasiveness of epithelial cells in vitro, properties required for tumor invasiveness and metastasis. Experimental evidence suggests that estrogens stimulate breast proliferation in hormone-dependent cells by upregulating an autocrine stimulatory loop involving epidermal growth factor receptor related tyrosine kinases (EGFR, erbB-2) (1,2). The erbB-2 oncogene product has been shown to be expressed in approximately 25–30% of breast cancer patients and has been correlated with poor prognosis and unfavorable survival rate (3,4). Frequently, patients whose tumors overexpress erbB-2 receptors do not respond well to conventional therapies, emphasizing the need for more aggressive therapies (5–7). Although the exact role of erbB-2 in tumor development has yet to be elucidated, tyrosine kinase mediated signal transduction appears to play an important role in breast cancer progression and metastasis.

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