[Resistance to antineoplastic treatments: mechanisms, clinical value]

Drug resistance is a major obstacle to successful chemotherapy for cancer. When it occurs, resistance to a wide range of agents is noted. Factors that rule this resistance can be defined as pharmacologic and cellular. Pharmacologic factors are those that prevent an adequate degree of tumor cell exposure and include considerations of dose and schedule of drugs. Cellular factors are those that imply the tumor cell itself and it is probable that multiple mechanisms co-exists: 1) the drug transport across the tumor cell membrane and the duration of the drug exposure, 2) the drug metabolism (activation, inactivation), 3) the cellular targets and the DNA repair processes. The pleiotropic multidrug resistance (mdr, mrp, lrp), alterations of a target enzyme (topoisomerase II, protein kinase C, glutathione S transferase, O6 alkylguanine-DNA alkyltransferase) and the protein modifications (heat shock protein, metallothioneins) are the principal mechanisms involved. Several methods have been established for the determination of the presence of these drug resistance mechanisms but variations in the results are observed with the different methods used. Therefore, the value and the relative importance of these mechanisms in human tumor resistance is not yet established. In the mean-time, strategies to prevent and to overcome this resistance are developed.