title: Gene amplification and altered enzymes as mechanisms for the development of drug resistance.
abstract: Two known mechanisms by which neoplastic cells may become resistant to chemotherapeutic agents are reviewed, using methotrexate (MTX) resistance as a model. These mechanisms are an increased level of target enzyme, found in several instances to be a consequence of gene amplification, or an altered target enzyme or receptor, less capable of binding the drug. An example of MTX resistance due to low-level gene amplification in leukemia cells from an MTX-resistant patient is described. Strategies for selectively eradicating these resistant cell populations may be formulated based on the mechanism by which these cells became drug-resistant.
mesh_terms: D000818:Animals; D004351:Drug Resistance; D005784:Gene Amplification; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate