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
Barton
J
J
AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Blackledge
G
G
Wakeling
A
A
D018033:Antibodies, Bispecific / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068818:Cetuximab; D066246:ErbB Receptors / Q000187:drug effects* / Q000502:physiology; D000077156:Gefitinib; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000068878:Trastuzumab
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000068878:Trastuzumab; D000068818:Cetuximab; D000077156:Gefitinib