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      Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer.

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          Abstract

          The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family that is abnormally activated in many epithelial tumors. Receptor activation leads to recruitment and phosphorylation of several downstream intracellular substrates, leading to mitogenic signaling and other tumor-promoting cellular activities. In human tumors, receptor overexpression correlates with a more aggressive clinical course. Taken together, these observations indicate that the EGFR is a promising target for cancer therapy. Monoclonal antibodies directed at the ligand-binding extracellular domain and low-molecular weight inhibitors of the receptor's tyrosine kinase are currently in advanced stages of clinical development. These agents prevent ligand-induced receptor activation and downstream signaling, which results in cell cycle arrest, promotion of apoptosis, and inhibition of angiogenesis. They also enhance the antitumor effects of chemotherapy and radiation therapy. In patients, anti-EGFR agents can be given safely at doses that fully inhibit receptor signaling, and single-agent activity has been observed against a variety of tumor types, including colon carcinoma, non-small-cell lung cancer, head and neck cancer, ovarian carcinoma, and renal cell carcinoma. Although antitumor activity is significant, responses have been seen in only a minority of the patients treated. In some clinical trials, anti-EGFR agents enhanced the effects of conventional chemotherapy and radiation therapy. Ongoing research efforts are directed at the selection of patients with EGFR-dependent tumors, identification of the differences among the various classes of agents, and new clinical development strategies.

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          Author and article information

          Journal
          J Clin Oncol
          Journal of clinical oncology : official journal of the American Society of Clinical Oncology
          American Society of Clinical Oncology (ASCO)
          0732-183X
          0732-183X
          Jul 15 2003
          : 21
          : 14
          Affiliations
          [1 ] University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA. jmendelsohn@mdanderson.org.
          Article
          JCO.2003.01.504
          10.1200/JCO.2003.01.504
          12860957
          ba22670d-f404-415e-88b5-2578ca5ccfc5

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