title: [New concepts for the study of anticancer drug resistance].
abstract: In the past decade, numerous mechanisms of resistance have been described, involving the availability of the drug at the target or the availability of the target itself, but resistance to cell death induction remains far from being understood. The involvement of p53, of Bcl2 and related proteins, of the Fas/Fas-L system and other membrane death receptor pathways, have especially been studied. However, conflicting results have been published concerning the impairment of apoptosis in resistance to cytotoxic drugs. This has shed important doubts on the currently accepted view, which presents apoptosis as a universal determinant of drug activity. These discrepancies are likely to be related to the cell-type specificity of apoptotic pathways and further research is warranted to get a complete picture of the role of cell death inhibition as a drug resistance mechanism. New genetic tools have been recently made available for the study of anticancer drug resistance. Differential or subtractive analyses of gene expression in drug-sensitive and drug-resistant cell lines or tumors have allowed the identification of genes which are potentially responsible for drug resistance, and which had not been recognized previously by the usual analytic approaches. The generation of genetic suppressor elements represents a more functional approach since they can be selected upon the actual resistance properties of the cell lines. Global transcriptome analysis can be performed through the use of cDNA microarrays, either for the comparison of drug-sensitive and resistant cell lines, or for the study of drug effects on gene expression. This may allow the identification of drug-response genes (whose expression is altered by the drug) and of signaling and metabolic pathways involved in drug activity.
authors.affiliation: Institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux Cedex, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D053222:Fas Ligand Protein; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
chemical_list: D002518:Ceramides; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor