Drug Resistance: New Approaches to Treatment

摘要: Mechanisms by which malignant cells may become resistant to chemotherapeutic agents are reviewed, with emphasis on methotrexate resistance. At least four mechanisms of resistance have been described in experimental systems, including human tumor propagated vitro: impaired uptake methotrexate, an altered target enzyme (dihydrofolate reductase), and elevated level dihydrofolate reductase, or decreased polyglutamylation. Combinations these changes noted occur acquiring methotrexate. In the clinic, examples due alteration reductase levels this gene amplification reported. A strategy for selectively eradicating second generation antifolates that cytotoxic is discussed.