Multidrug resistance, gene therapy

Shuhendler AJ, Chung R, Manias J, Connor A, Rauth AM, Wu XY. A novel doxombidn-mitomycin C co-encapsulated nanoparticle formulation exhibits anti-cancer synergy in multidrug resistant human breast cancer cells. Breast Cancer Res Treatment, submitted in 2008. Dass CR, Choong PFM. Selective gene delivery for cancer therapy using cationic liposomes In vivo proof of applicability. J Control Release 2006 113 155-163. 

The protease inhibitors are used in the multidrug therapy of HIV infection. Resistance to the HIV protease inhibitors results from mutations in the protease gene and perhaps the cleavage sites of gag-pol. Although different protease mutations tend to be associated with resistance to individual drugs, resistance to one protease inhibitor is often associated with a less than optimal response to other agents of this class. Indinavir, ritonavir, and lopinavir require more mutations to lose their effectiveness than do the other protease inhibitors. 

MDR transporters are usually encoded by housekeeping genes as normal constituents of bacterial chromosome and are present in the whole population of a given bacterial species. The basal level of expression of nonspecific multidrug efflux pumps in wild-type cells determines the basal level of antibiotic susceptibility. This innate resistance may still be low enough such that bacteria are susceptible to therapy with a given antibiotic. 

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