Biochemical and Clinical Implications of the ErbB/HER Signaling Network of Growth Factor Receptors

https://doi.org/10.1016/S0065-230X(08)60784-8Get rights and content

Publisher Summary

Carcinoma, cancer of epithelial cells, is a major cause of morbidity and mortality. Clonal fixation and propagation of oncogenic genetic changes, sporadically accumulating in epithelial cells, depend on growth factors and their surface receptors. ErbB tyrosine kinases are one of the large families of receptors that bind multiple neuregulins and other epidermal growth factor-like molecules. Certain ErbB members and their ligands are involved in human cancers of various origins. Several biochemical attributes enable ErbB-2 to act as an epithelial cell amplifier of stroma-derived growth factor signals. It delays ligand dissociation, enhances coupling to the mitogen-activated protein kinase pathway, and impedes the rate of receptor downregulation. The realization that ErbB-2 is a master regulator of a signaling network that drives epithelial cell proliferation identifies this protein as a target for cancer therapy. Various ErbB-2-directed therapeutic approaches, including immunological and genetic therapies, demonstrate promising clinical potential.

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