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

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, including ATP-requiring enzymes (ATPases). Among these ATPases, 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 their mechanism in 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.

Automated summary

Multidrug resistance (MDR) refers to the phenomenon where tumor cells become unresponsive to one or more chemotherapeutic drugs during or after treatment. This critically limits treatment outcomes and poses a major challenge for clinicians. Alterations in intracellular drug concentration through the modulation of drug transport across the plasma membrane is the main cause of MDR, and this process involves various mediators, including ATP-requiring enzymes (ATPases). Among these ATPases, ABC transporters have been extensively studied and found to be highly implicated in tumorigenesis and MDR. This review focuses on the effects of retinoids on ABC enzymes and aims to understand their mechanism in combating cancer cell resistance.