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癌症中的醛脱氢酶:生物标志物和药物开发的契机?

Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development?

作者信息

Pors Klaus, Moreb Jan S

机构信息

Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK.

Hematological Malignancies, PO Box 100278, Gainesville, FL 32610-0277, USA.

出版信息

Drug Discov Today. 2014 Dec;19(12):1953-63. doi: 10.1016/j.drudis.2014.09.009. Epub 2014 Sep 26.

Abstract

Aldehyde dehydrogenases (ALDHs) belong to a superfamily of 19 isozymes that are known to participate in many physiologically important biosynthetic processes including detoxification of specific endogenous and exogenous aldehyde substrates. The high expression levels of an emerging number of ALDHs in various cancer tissues suggest that these enzymes have pivotal roles in cancer cell survival and progression. Mapping out the heterogeneity of tumours and their cancer stem cell (CSC) component will be key to successful design of strategies involving therapeutics that are targeted against specific ALDH isozymes. This review summarises recent progress in ALDH-focused cancer research and discovery of small-molecule-based inhibitors.

摘要

醛脱氢酶(ALDHs)属于一个由19种同工酶组成的超家族,已知其参与许多重要的生理生物合成过程,包括特定内源性和外源性醛底物的解毒。越来越多的ALDHs在各种癌症组织中高表达,这表明这些酶在癌细胞的存活和进展中起关键作用。明确肿瘤及其癌症干细胞(CSC)成分的异质性,将是成功设计针对特定ALDH同工酶的治疗策略的关键。本综述总结了以ALDH为重点的癌症研究以及小分子抑制剂发现方面的最新进展。

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