Gefitinib (Iressa) in oncogene-addictive cancers and therapy for common cancers

Abstract

Activating mutations in the epidermal growth factor receptor (EGF-R) predict response to gefitinib. How does this recent discovery affect our outlook on selective (targeted) cancer therapy? It allows us to compare mutant EGF-R with Bcr-Abl as anticancer drug targets and to discuss the nature of oncogene addiction. It emphasizes molecular diagnostics to identify oncogene-addictive cancers. It also re-enforces the notion that most cancers with multiple oncogenic alterations (common cancers) will unlikely respond to selective drugs alone. In such cancers, one strategy is targeting cancer-non-specific, universal and vital structures, essential for life of all cells: microtubules, topoisomerases, histone deacetylases, the proteasome. But in order to be cancer-selective, these chemotherapeutic agents need to be combined with selective agents. Such combinations can be effective and selective in common cancers. ©2004 Landes Bioscience.