P-glycoprotein mediated multidrug resistance and its implications for pathology.
The discovery of P-glycoprotein has revealed a fundamental mechanism by which cancer cells evade chemotherapy and this principle has proven relevant to general cellular defence mechanisms in normal physiology. To date this knowledge has promised to improve current cancer chemotherapy through the manipulation of drug combinations according to the P-glycoprotein status of the tumor. Furthermore, the discovery of inhibitors of the protein may provide new therapeutic tools in the treatment of multidrug resistant neoplasia, provided the benefits are deemed greater than the potential detrimental side effects. When looking towards future therapies, however, we must also consider additional mechanisms which undoubtedly contribute to clinical drug resistance. Complete elucidation of this complex cellular defence network will hopefully translate into therapeutic opportunities to circumvent all mechanisms of multidrug resistance, thus positively impacting on patient survival.
Trambas
C M
CM
Division of Pathology, University of Tasmania, Hobart, Australia.
Muller
H K
HK
Woods
G M
GM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1