Aldehyde dehydrogenases (ALDHs) are highly expressed in the chemotherapy- and radiotherapy-resistant cell subpopulations of many different cancer types. Accordingly, the development of ALDH inhibitors may be the most direct approach to target these cell populations. However, inhibiting multiple ALDH family members can be toxic and isoform-specific inhibition is often ineffective. This review discusses the role of ALDH in cancer and therapy resistance, and then overviews the various available ALDH inhibitors with a focus on the clinical potential and limitations of these agents as cancer therapeutics. Finally, challenges and future research directions to effectively target ALDH in the management of cancer therapy resistance are discussed.
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