Aldehyde Dehydrogenase Inhibitors for Cancer Therapeutics

Saketh S Dinavahi; Christopher G Bazewicz; Raghavendra Gowda; Gavin P Robertson

doi:10.1016/j.tips.2019.08.002

Aldehyde Dehydrogenase Inhibitors for Cancer Therapeutics

Trends Pharmacol Sci. 2019 Oct;40(10):774-789. doi: 10.1016/j.tips.2019.08.002. Epub 2019 Sep 9.

Authors

Saketh S Dinavahi¹, Christopher G Bazewicz², Raghavendra Gowda³, Gavin P Robertson⁴

Affiliations

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.

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

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aldehyde Dehydrogenase / antagonists & inhibitors*
Aldehyde Dehydrogenase / metabolism
Animals
Enzyme Inhibitors / pharmacology*
Enzyme Inhibitors / therapeutic use
Humans
Neoplasms / drug therapy*
Neoplasms / enzymology*

Substances

Enzyme Inhibitors
Aldehyde Dehydrogenase