Integrins and extracellular matrix: a novel mechanism of multidrug resistance.
Multidrug resistance remains the major hurdle to successful cancer treatment. Classical mechanisms of multidrug resistance include drug efflux pumps, glutathione-S-transferase upregulation and topoisomerase II-associated multidrug resistance. However, despite extensive research, the clinical relevance of these mechanisms remains unclear and no significant clinical benefit has materialized. Recently, a novel mechanism of multidrug resistance has been identified--extracellular matrix-mediated multidrug resistance: integrin-mediated adherence of cells to extracellular matrix proteins results in significant resistance to many anticancer agents that induce cell death via unrelated mechanisms. Verification of the mechanisms of action of this novel phenomenon will hopefully identify new therapeutic targets to aid in the fight against cancer.
Elliott
Tony
T
Centre for Inflammation Research, University of Edinburgh, Scotland, UK. Tony.Elliott@ed.ac.uk
Sethi
Tariq
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy*; D015290:Second Messenger Systems / Q000187:drug effects
D000970:Antineoplastic Agents; D016023:Integrins