Consequences of the resistance to drug-induced topoisomerase II-mediated DNA cleavage.
A rapid and accurate quantitative clinical assay that could predict the likelihood of response of an individual patient's cancer to chemotherapy would be invaluable. The assay's identification of active agents would ensure the patient of the greatest benefit from therapy. Identification of inactive agents would spare the patient unnecessary toxic effects of the drugs. Development of such an assay necessitates the identification of drug targets, the ability to measure the drug-target interaction in clinical samples, and the knowledge that measurement of the drug-target interaction is associated with the mechanism by which the drug kills malignant cells. Focusing on drugs that target topoisomerases, my laboratory has begun to develop such an assay based upon studies in human leukemia cell lines exhibiting different sensitivities to topoisomerase-reactive drugs. The focus of this paper is the basic research that supports the clinical approach we are taking.
M.D. Anderson Cancer Center, Department of Medical Oncology, University of Texas, Houston 77030.
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000187:drug effects* / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007938:Leukemia / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II