Small-molecule tyrosine kinase inhibitors as radiosensitizers

Abstract

The discovery of a class of highly selective and potent compounds called the 4-anilinoquinazolines has led to the development of small-molecule tyrosine kinase inhibitors as potential anticancer agents. These agents inhibit essential cellular pathways in growth factor expression and can be administered as an oral formulation. Some of these agents, such as ZD1839 and OSI-774, tend to bind in vitro only to the epidermal growth factor receptor tyrosine kinase while others, such as CI-1033, bind to multiple members of the ErbB family. The first clinical compounds that were developed, such as ZD1839, were reversible inhibitors. More recently, irreversible compounds have been developed that may be more effective at producing long-term suppression. Very little published work is available concerning the interaction of small-molecule tyrosine kinase inhibitors with radiation. This article presents our data on the interactions of CI-1033 with radiation.