Abstract :Despite the major progresses in biomedical research and the development of novel therapeutic strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is over expression of members of the family of ATP-binding cassette (ABC) transporters [1,2]. These transporters use energy derived from the hydrolysis of ATP to transport a wide range of substrates (endogenous toxicants and xenobiotics but also chemotherapeutic agents) across biological membranes against a concentration gradient. Since the discovery that the over expression of ABC transporters in cancer cells can mediate resistance to anti-cancer drugs, research has been directed towards developing compounds that inhibit the efflux activity of ABC transporters and increase classical chemotherapy efficacy. However, to date, the Food and Drug Administration (FDA) has not approved the use of any ABC transporter inhibitor due to toxicity issues [3,4].