Abstract
Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. In order to overcome the MDR, pharmacologically active compounds, designated MDR modulators or chemosensitizers, may circumvent the “classical” MDR phenotype by inhibiting the efflux pump activity of P-glycoprotein. One obstacle in applying MDR modulators arises from their commonly occurring intrinsic toxicity at doses necessary to be active, e.g. hear failure, hypotension, hyperbilirubinemia, and immunosupression. Additionally, tumor cells can develop resistance against the applied chemosensitizers, so-called tertiary resistance. Consequently, it is necessary to develo palternative, less toxic and more efficient strategies to overcome MDR. Such an alternative procedure to circumvent P-glycoprotein mediated MDR in cancer cells is to prevent the biosynthesis of P-glycoprotein by selective blocking the expression the MDRI mRNA. In this article, we shall focus on the progress of novel gene therapy system against the MDR.
