The DNA damage response to monofunctional anticancer DNA binders

Combinations of different experimental modalities including yeast, mammalian cells, xenografts and in silico models have proved useful in elucidating the mechanism of action of novel anticancer agents including covalent DNA binders like the ecteinascidins (trabectedin/yondelis, zalypsis and PM01183) and to characterize their influence on tumor cell biology. The experimental models can also lead to identification of predictive markers and provide a rational for development of more efficient/less toxic drug combinations, thereby facilitating clinical development.