Overcoming of P-glycoprotein-mediated multidrug resistance of tumors in vivo by drug combinations

Publication date: September 2014 Source:Synergy, Volume 1, Issue 1 Author(s): Mohamed Saeed , Maen Zeino , Onat Kadioglu , Manfred Volm , Thomas Efferth Inhibition of P-glycoprotein represents an attractive possibility to modulate resistance of cancer cells to anticancer drugs. One major strategy to overcome P-glycoprotein-mediated multidrug resistance (MDR) of tumors is to increase intracellular concentrations of anticancer drugs. This can be achieved by blocking of P-glycoprotein-mediated drug efflux using synthetic or natural small molecules or monoclonal antibodies, which bind to various parts of the efflux channel. Another possibility to increase intracellular drug concentrations can be reached by nanoparticles. A further major strategy to overcome MDR involves the downregulation of P-glycoprotein expression either by therapeutic nucleic acids (antisense oligodeoxynucleotides, RNA interference) or by small molecule inhibitors of signal transduction kinases that govern P-glycoprotein expression (e.g. PI3K/Akt inhibitors). In the present review, we give a critical overview on in vivo experiments using murine syngeneic and human xenograft tumors. Strengths and weaknesses of in vivo experiments are critically discussed to further explore and utilize the full potential of animal experiments for better determination of requirements for successful clinical trials on MDR reversal in the future.
Source: Synergy - Category: Molecular Biology Source Type: research