Chapter Five - ATP-Dependent Chromatin Remodeling Complexes as Novel Targets for Cancer Therapy

Abstract

The progression to advanced stage cancer requires changes in many characteristics of a cell. These changes are usually initiated through spontaneous mutation. As a result of these mutations, gene expression is almost invariably altered allowing the cell to acquire tumor-promoting characteristics. These abnormal gene expression patterns are in part enabled by the posttranslational modification and remodeling of nucleosomes in chromatin. These chromatin modifications are established by a functionally diverse family of enzymes including histone and DNA-modifying complexes, histone deposition pathways, and chromatin remodeling complexes. Because the modifications these enzymes deposit are essential for maintaining tumor-promoting gene expression, they have recently attracted much interest as novel therapeutic targets. One class of enzyme that has not generated much interest is the chromatin remodeling complexes. In this review, we will present evidence from the literature that these enzymes have both causal and enabling roles in the transition to advanced stage cancers; as such, they should be seriously considered as high-value therapeutic targets. Previously published strategies for discovering small molecule regulators to these complexes are described. We close with thoughts on future research, the field should perform to further develop this potentially novel class of therapeutic target.