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.
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.
Trends Pharmacol Sci. 2019 Oct;40(10):774-789. doi: 10.1016/j.tips.2019.08.002. Epub 2019 Sep 9.
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.
醛脱氢酶（ALDHs）在许多不同类型癌症的化疗和放疗耐药细胞亚群中高度表达。因此，开发 ALDH 抑制剂可能是针对这些细胞群体的最直接方法。然而，抑制多个 ALDH 家族成员可能有毒性，同工酶特异性抑制通常无效。本综述讨论了 ALDH 在癌症和治疗耐药中的作用，然后概述了各种可用的 ALDH 抑制剂，重点介绍了这些药物作为癌症治疗剂的临床潜力和局限性。最后，讨论了有效靶向癌症治疗耐药性中 ALDH 所面临的挑战和未来研究方向。
