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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/33360

Title: Mitochondria-targeted Doxorubicin is Active and Resistant to Drug Efflux
Authors: Chamberlain, Graham Ross
Advisor: Kelley, Shana O.
Department: Pharmaceutical Sciences
Keywords: Doxorubicin
Drug Resistance
P-glycoprotein
Drug Efflux
Topoisomerase II
Mitochondria
Mitochondria Penetrating Peptides
Issue Date: 21-Nov-2012
Abstract: Several families of highly effective anticancer drugs are selectively toxic to cancer cells because they interfere with nucleic acids synthesis. Many such drugs are pumped out of cells faster than they can reach their targets, which limits efficacy and renders many tumors drug-resistant. By delivering a drug to the mitochondria of mammalian cells – an organelle where nucleic acids synthesis also occurs – efflux could be prevented through sequestration. Doxorubicin, a topoisomerase II inhibitor, was used as proof-of-principle for this concept due to its susceptibility to resistance. When doxorubicin is attached to a peptide that specifically targets mitochondria, its efficacy is not attenuated by various resistance mechanisms to which doxorubicin is normally susceptible. These results indicate that targeting drugs to the mitochondria provides a means to evade the most common mechanism of drug resistance.
URI: http://hdl.handle.net/1807/33360
Appears in Collections:Master

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