MDR1/P-glycoprotein expression in colorectal cancer

Drug resistance to multiple chemotherapeutic agents is considered a major cause of chemotherapy failure. An extensively studied and relatively well understood type of cellular drug resistance is P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Pgp acts as an energy-dependent drug efflux pump, thereby decreasing the intracellular drug concentration and causing drug resistance, in in vitro experiments. Colorectal cancer and colorectal mucosa generally express high levels of Pgp, and this may contribute to the general unresponsiveness of colorectal cancer to natural product, anticancer drugs. The controversies concerning the prognostic role of Pgp expression and its contribution to tumour aggressiveness, and possible reasons for the disappointing results of clinical MDR reversal trials in colorectal cancer are discussed.