Use of retinoic acid/aldehyde dehydrogenase pathway as potential targeted therapy against cancer stem cells.

A large number of studies have investigated possible drug resistance mechanisms of cancer cells and suggested strategies to overcome it. In this review, we outline the role and function of aldehyde dehydrogenase (ALDH) activity in multiple cellular functions and in cancer stem cells (CSCs) and focus on the role of retinoic acid (RA), one of the products of ALDH isozymes. We discuss our observation that ATRA and other RAs can suppress ALDH activity and decrease different ALDH isozyme proteins and result in detrimental effects on cell proliferation, invasion and chemotherapy sensitivity. We review the known uses of different RAs in the treatment of cancers. We review the use of RAs in combination with chemo-/radiotherapy and the major signaling pathways affected in different tumor types. We provide follow-up on studies that may have used our prior observation with the aim of targeting the CSCs. We conclude with summary of the findings and potential impact of published studies on future use of RAs in the targeting of CSCs and drug resistance.