Aldehyde dehydrogenase (ALDH) is an enzyme that participates in important cellular
mechanisms as aldehyde detoxification and retinoic acid synthesis; moreover, ALDH activity is involved
in drug resistance, a characteristic of cancer stem cells (CSCs). Even though ALDH is found in
stem cells, CSCs and progenitor cells, this enzyme has been successfully used to identify and isolate
cell populations with CSC properties from several tumor origins.
ALDH is allegedly involved in cell differentiation through its product, retinoic acid. However, direct or
indirect ALDH inhibition, using specific inhibitors or retinoic acid, has shown a reduction in ALDH
activity, along with the loss of stem cell traits, reduction of cell proliferation, invasion, and drug sensitization.
For these reasons, ALDH and retinoic acid are promising therapeutic targets.
This review summarizes the current evidence for ALDH as a CSCs marker in solid tumors, as well as
current knowledge about the functional roles of ALDH in CSCs. We discuss the controversy of ALDH
activity to maintain CSC stemness, or conversely, to promote cell differentiation. Finally, we review
the advances in using ALDH inhibitors as anti-cancer drugs.