Gene Therapeutic Approaches to Overcome ABCB1-Mediated Drug Resistance.

Abstract

Multidrug resistance (MDR) to pharmaceutical active agents is a common clinical problem in patients suffering from cancer. MDR is often mediated by over expression of trans-membrane xenobiotic transport molecules belonging to the superfamily of ATP-binding cassette (ABC)-transporters. This protein family includes the classical MDR-associated transporter ABCB1 (MDR1/P-gp). Inhibition of ABC-transporters by low molecular weight compounds in cancer patients has been extensively investigated in clinical trials, but the results have been disappointing. Thus, in the last decades alternative experimental therapeutic strategies for overcoming MDR were under extensive investigation. These include gene therapeutic approaches applying antisense-, ribozyme-, RNA interference-, and CRISPR/Cas9-based techniques. Various delivery strategies were used to reverse MDR in different tumor models in vitro and in vivo. Results and conclusions of these gene therapeutic studies will be discussed.