Human deoxyribonucleic acid topoisomerases: molecular targets of anticancer drugs.
Mammalian cells contain two distinct types of topoisomerases. They have been mechanistically classified into a type I (topo I) and type II (topo II) enzyme. Anticancer drugs which target topo I include camptothecin, irinotecan, topotecan, and 9-aminocamptothecin. Anticancer drugs which target topo II include etoposide, mitoxantrone, teniposide, and doxorubicin. Much experimental work has indicated that cells with high topoisomerase are drug sensitive, and cells with low topoisomerase are drug resistant. These data suggest that patients whose tumors have abundant topoisomerase might be predicted to respond to topo targeted anticancer drugs. In order to test this hypothesis, immunohistochemical stains have been developed which can recognize the topoisomerases in formalin-fixed, paraffin-embedded, human tissue sections. This may make it feasible to correlate topoisomerase expression in human cancers with clinical response to chemotherapy.
Holden
J A
JA
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division; D004264:DNA Topoisomerases, Type I / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II