Multidrug resistance pathways (MDR)

Multidrug resistance (MDR) pathways refer to the complex network of cellular mechanisms that allow cells, particularly cancer cells and pathogens, to survive exposure to a wide variety of structurally and functionally diverse drugs (NIH, 2018). These pathways primarily involve the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (ABCB1), which actively efflux chemotherapeutic agents out of the cell to maintain sub-therapeutic intracellular concentrations (EBI, 2025). Other mechanisms include enhanced DNA repair systems, evasion of apoptosis, and metabolic detoxification by enzymes like glutathione S-transferases (ResearchGate, 2013). While these pathways are critical for protecting normal tissues from toxins, their activation in disease states presents a major therapeutic challenge, leading to treatment failure and disease progression (Nature Reviews Cancer, 2018). Pharmacological strategies to target these pathways involve the use of chemosensitizers or inhibitors designed to restore drug sensitivity, although clinical success has been limited by toxicity and the redundancy of resistance mechanisms (Frontiers in Pharmacology, 2021). In addition to cancer, MDR pathways are critical in infectious diseases, where they mediate resistance to antibiotics, antivirals, and antimalarials through similar efflux and metabolic mechanisms (NIH, 2002).

Other names

MDR mechanismsChemoresistance pathwaysDrug efflux pathwaysPleiotropic drug resistance

Inhibition of ATP-binding cassette (ABC) transporters, competitive inhibition of drug efflux, modulation of ATPase activity, and transcriptional downregulation of MDR-related genes.