Epidermal growth factor receptor-targeted therapy in colorectal cancer.
Advanced colorectal carcinoma is a major cause of morbidity and mortality in the United States and other developed countries. Thus, new therapeutic strategies are urgently needed. The expression of various growth factors, growth inhibitors, and their receptors contributes to the development of colorectal cancer as well as to the proliferation and survival of malignant cells. Approximately 65% to 70% of human colon carcinomas have been shown to express the epidermal growth factor receptor (EGFR). Several investigators have reported that EGFR expression correlates with more aggressive disease and a poorer prognosis. Epidermal growth factor receptor plays a crucial role in initiating signal transduction; thus, strategies directed towards interruption of this signaling pathway have been shown to impair tumor cell proliferation. These include anti-EGFR monoclonal antibodies, immunotoxin conjugates, and EGFR tyrosine kinase inhibitors. Preclinical and clinical trials using these new therapeutic modalities appear promising in the treatment of colorectal cancer and are reviewed in this article.
O'dwyer
Peter J
PJ
University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA.
Benson
Al B
AB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000068818:Cetuximab; D000077156:Gefitinib