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Trends Pharmacol Sci. 2019 Sep 9. pii: S0165-6147(19)30185-3. doi: 10.1016/j.tips.2019.08.002. [Epub ahead of print]

Aldehyde Dehydrogenase Inhibitors for Cancer Therapeutics.

Author information

1
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma and Skin Cancer Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
2
Department of Dermatology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma and Skin Cancer Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
3
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma and Skin Cancer Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma Therapeutics Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Foreman Foundation for Melanoma Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
4
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Department of Dermatology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Department of Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma and Skin Cancer Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Melanoma Therapeutics Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Foreman Foundation for Melanoma Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. Electronic address: gpr11@psu.edu.

Abstract

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.

KEYWORDS:

aldehyde dehydrogenase; cancer pharmacology; cancer resistance; cancer stem cells; cancer therapy; targeted inhibitors

PMID:
31515079
DOI:
10.1016/j.tips.2019.08.002

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