Resistance of mammalian tumour cells to anticancer drugs: mechanisms and concepts relating specifically to methotrexate and vincristine.
The predominant mechanisms of resistance to antitumour drugs which have been identified in mammalian cells are reviewed. Experimental evidence from in-vitro studies is then presented, indicating that for methotrexate the main mechanism(s) of resistance appear to reflect the level of resistance expressed and may depend on the manner in which such resistance develops or is induced, and for vincristine, in two independently derived resistant sublines, resulting from exposure either to fractionated X-irradiation or continuously to vincristine, significantly different characteristics are expressed, implicating different resistance mechanisms. These experimental observations, if confirmed, have major implications for the drug treatment of human 'solid' tumours.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014750:Vincristine; D008727:Methotrexate