A Review of Small-Molecule Epidermal Growth Factor Receptor-Specific Tyrosine Kinase Inhibitors in Development for Non-Small Cell Lung Cancer

Overexpression of the epidermal growth factor receptor is commonly seen in a variety of epithelial tumors including lung cancer, and it is particularly common in the non-small cell histologic variant. Despite intense research efforts, therapeutic advances to date have failed to result in a significant survival benefit for patients with advanced disease. The lack of overall survival benefit and high toxicity associated with cytotoxic chemotherapy indicates the need for novel therapies that have a favorable effect on survival with minimal toxicity. Greater understanding of molecular biology and the intricate cellular pathways has resulted in the development of a new field of targeted therapeutics that will arrest dysregulated cell growth in malignant cells. Tyrosine kinases represent an important category of signaling proteins that catalyze phosphorylation of tyrosine residues leading to reactions ultimately resulting in cell growth, differentiation, proliferation, and death. Inhibition of tyrosine kinase activity represents a logical targeted approach in malignancies with overexpression of tyrosine kinase. Several small-molecule epidermal growth factor receptor tyrosine kinase inhibitors have been developed and are currently undergoing clinical trials. This article will review several of these agents as well as their role in the treatment of non-small cell lung cancer.