The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

Simple Summary Cancer stem cells (CSCs) are an engine of tumor progression and a source of tumor therapy resistance and regrowth after treatment. Modern conventional therapies can eliminate most non-CSCs, while CSCs often survive cancer treatment, leading to tumor relapse and metastases. Prostate cancer (PCa) is a disease that affects 1 in 8 men in their lifetime. Although the 5-year survival rate of patients with localized or regional PCa is close to 100%, it dramatically decreases to 30% for the patients with distant metastases. Thus, targeting CSCs might be a promising approach to overcome tumor resistance and increase the efficiency of the current cancer treatment strategies. A high aldehyde dehydrogenase (ALDH) activity is a widely accepted marker of prostate CSCs. This review discusses the current state of research regarding the role of individual ALDH enzymatic proteins in PCa development and progression, their possible therapeutic targeting, and future development in this field. 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 metastases. 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 dehydrogenase activity (ALDH) is widely accepted for prostate cancer (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 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay 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.