NOVEL STRATEGIES AGAINST MULTIDRUG RESISTANCE MEDIATED BY P-GLYCOPROTEIN

P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) protein that mediates the ATP-dependent efflux of hydrophobic toxins. Physiologically, P-gp excretes endogenous metabolites and other xenotoxic substrates into the urine, bile and feces. P-gp is a multidrug resistance (MDR) pump, which exports chemotherapeutic agents from target cells to the extracellular space. P-gp is considered an adverse factor in the prognosis of hematological and solid tumors because efflux of chemotherapeutic drugs reduces their intracellular levels, requiring higher doses to produce an effect equivalent to that before the P-gp overexpression. Effective P-gp modulators must inhibit P-gp activity, avoiding pharmacological interactions and toxicity. Nanoparticle-based advanced delivery systems have been recently studied, showing that these novel strategies can overcome MDR in some cancers.