Tumor p53 status and response to topoisomerase II inhibitors.

Abstract

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". Topoisomerase II (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 different 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.

• Authors: Nikola I Valkov, Daniel M Sullivan
• Journal: Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy (Drug Resist Updat) Vol. 6 Issue 1 Pg. 27-39 (Feb 2003) ISSN: 1368-7646 [Print] Scotland
• PMID: 12654285 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Topoisomerase II Inhibitors
• Tumor Suppressor Protein p53

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Humans
• Neoplasms (drug therapy, metabolism)
• Topoisomerase II Inhibitors
• Tumor Suppressor Protein p53 (biosynthesis, genetics)