The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

: Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation- and drug-resistant, leading to tumor relapse and metastasis. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde de-hydrogenase activity (ALDH) is widely accepted for PCa and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting BODIPY aminoacetaldehyde (BAAA) into the fluorescent product BOD-IPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, a mutual functional interplay between them also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.