EGFR antagonists in cancer treatment.

Cancer cells may acquire the capacity for autonomous and dysregulated proliferation through the uncontrolled production of specific molecules that promote cell growth (growth factors) or through abnormal, enhanced expression of specific proteins (growth factor receptors) on the cell membranes to which growth factors selectively bind. Both processes trigger a series of intracellular signals that ultimately lead to the proliferation of cancer cells, induction of angiogenesis, and metastasis.1 The majority of human epithelial cancers are marked by functional activation of growth factors and receptors of the epidermal growth factor receptor (EGFR) family. Given this phenomenon, EGFR was the first growth factor receptor to be proposed as a target for cancer therapy. After 20 years of drug development, four EGFR antagonists are currently available for the treatment of four metastatic epithelial cancers: non–small-cell lung cancer, squamous-cell carcinoma of the head and neck, colorectal cancer, and pancreatic cancer. Less information is available about the use of EGFR antagonists in the treatment of earlier stages of cancer. This article summarizes the mechanisms of action of EGFR inhibitors, presents the clinical evidence of their anticancer activity, and considers the current, and controversial, clinical issues with respect to their optimal use in the treatment of patients with cancer.