Acquired versus intrinsic resistance to methotrexate: diversity of the drug-resistant phenotype in mammalian cells.
The expression of resistance by tumor cells to anticancer drugs remains a primary cause of patient failure to chemotherapeutic intervention in cancer. Although studied for many years, both the acquisition and maintenance of drug resistance continue to provide active areas for research and the application of modern molecular and cell biological techniques to those questions has begun to generate a wealth of new information. This article attempts to summarize and contrast some of the more recent observations concerning acquired and intrinsic resistance to the classical antifolate methotrexate, and suggests that the mechanisms of intrinsic resistance, and to a lesser extent acquired resistance as well, may be more broad based than previously thought and that the expression of intrinsic resistance may be strongly influenced by physiological and genetic variation.
Melera
P W
PW
Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201.
D000818:Animals; D006224:Cricetinae; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D013762:Tetrahydrofolate Dehydrogenase / Q000502:physiology
C010920:dihydrofolate; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate