Growth factors and their receptors: new targets for prostate cancer therapy.

Stimulation of the signal transduction pathway of the epidermal growth-factor receptor (EGFR) tyrosine kinase family of receptors in tumor cells enhances cellular proliferation, prevents apoptosis, and promotes tumor-cell mobility, adhesion, and invasion. Therapeutic approaches used to target the EGFR and its signal transduction cascade include (1) monoclonal antibodies (eg, cetuximab [IMC-C225]) directed against the extracellular binding domain of the receptor; and (2) trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer. Antisense strategies are in preclinical development. Low-molecular-weight inhibitors of the EGFR tyrosine kinase also in clinical development include OSI-774, PD182905, PKI-166, CI-1033, and ZD1839. ZD1839 has shown encouraging results in patients with prostate cancer in phase 1 trials. mn