The potential roles of retinoids in combating drug resistance in cancer: Implications of ATP-binding cassette (ABC) transporters

Abstract

Multidrug resistance (MDR) means that tumour cells become unresponsive during or after the course of treatment to one or more of chemotherapeutic drugs. Chemotherapeutic resistance critically limits the treatment outcomes and remains a key challenge for clinicians. The alternation in intracellular drug concentration through the modulation of its transport across the plasma membrane is the major cause for MDR and is adopted by various mediators, includingATP-requiring enzymes (ATPases).Among theseATPases,ABC transporters have been extensively studied, and found to be highly implicated in tumorigenesis and MDR. The present review sheds light on the documented effects of retinoids on ABC enzymes to understand theirmechanismin combating cancer cell resistance. This would open the gate to test the mechanism and applicability of different new synthetic retinoids in literature and market as modulators of ATP-dependent efflux pumping activity, and promote their applicability in diminishing anti-cancer drug resistance.