Multidrug resistance in cancer or inefficacy of neuroactive agents: innovative strategies to inhibit or circumvent the active efflux transporters selectively

Multidrug resistance (MDR) is a crucial issue in the treatment of cancer cells that protect themselves by overexpression of active efflux transporters (AETs). AET expression maintains the homeostasis in healthy tissues and in the blood-brain barrier it often prevents drugs from reaching the brain. Inhibition of AETs could therefore be a valuable solution for preventing MDR; but nonselective long-term AET blocking can be harmful toward healthy tissues and, in particular, the brain. This review looks at the development of innovative formulations suitable for selectively blocking or avoiding AETs as promising ways to overcome the challenges of MDR and inefficacy of neuroactive agents.