Resistance in cancer: a target for drug discovery.
Resistance remains a major problem in the clinical utility of cancer chemotherapy. However, it also represents a tumour cell phenotype that is in many ways different, and thus distinguishable, from the majority of normal cells. Two approaches to the targeting of resistant cells are described involving intratumoral P450 expression, mechanisms of drug-efflux and defective DNA repair. It is suggested that the view of the solid tumour as a complex organ rather than a collection of individual cells will inform future drug development and both overcome and target multiple resistance mechanisms.
Searcey
Mark
M
Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK mark.searcey@ulsop.ac.uk
Patterson
Laurence H
LH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy; D010100:Oxygen / Q000737:chemistry; D013997:Time Factors
D000970:Antineoplastic Agents; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen