Tumor p53 status and response to topoisomerase II inhibitors

It is thought that when tumor cells are treated with anticancer drugs, they die through the apoptotic pathway and that cell resistance to cancer chemotherapy is mainly a resistance to apoptosis commitment. p53 is not functional in nearly half of the tumors examined and because of its involvement (directly or through its target genes) in the apoptotic pathway, drug resistance to chemotherapy has been largely attributed to the status of this "tumor suppressor protein". TopoisomeraseII (topo II) inhibitors are widely used not only as single agents, but also in the majority of combination treatment protocols for hematologic malignancies and solid tumors. The relationship between p53 and topo II raises many questions about basic regulatory, biochemical, structural and functional characteristics that could be different in cells in diferent tissues, and most importantly, between different tumor cell types and their normal tissue counterpart. Understanding these relationships may lead to strategies for chemotherapy optimization and further precision targeting of tumor cells in order to avoid drug resistance and thereby chemotherapy failure. (C) 2003 Elsevier Science Ltd. All rights reserved.