A comprehensive comparative study on LSD1 in different cancers and tumor specific LSD1 inhibitors

Jianshu Dong; Waqar Pervaiz; Bilal Tayyab; Dié Li; Lei Kang; Huimin Zhang; Huimin Gong; Xinli Ma; Jian Li; Clement Agboyibor; Yuefeng Bi; Hongmin Liu

doi:10.1016/j.ejmech.2022.114564

A comprehensive comparative study on LSD1 in different cancers and tumor specific LSD1 inhibitors

Eur J Med Chem. 2022 Oct 5:240:114564. doi: 10.1016/j.ejmech.2022.114564. Epub 2022 Jun 28.

Authors

Jianshu Dong¹, Waqar Pervaiz², Bilal Tayyab², Dié Li², Lei Kang², Huimin Zhang², Huimin Gong², Xinli Ma³, Jian Li³, Clement Agboyibor⁴, Yuefeng Bi⁵, Hongmin Liu⁶

Affiliations

¹ School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Henan Province for Drug Quality Control and Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: jdong@zzu.edu.cn.
² School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Henan Province for Drug Quality Control and Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China.
³ China-US(Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, Henan, 450008, China.
⁴ Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China.
⁵ School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of Henan Province for Drug Quality Control and Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China; Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: zzubyf@126.com.
⁶ Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: liuhm@zzu.edu.cn.

PMID: 35820351
DOI: 10.1016/j.ejmech.2022.114564

Abstract

LSD1 was significantly over-expressed in several cancer types, and its aberrant overexpression was revealed to play a crucial role in the initiation and progression of cancer. Several LSD1 inhibitors that were discovered and developed so far were found to be effective in attenuating tumor growth in both in vivo and in vitro studies. However, the major challenge associated with the development of cancer therapies is personalized treatment. Therefore, it is essential to look in detail at how LSD1 plays its part in carcinogenesis and whether there are any different expression levels of LSD1 in different tumors. Here in this review, fresh insight into a list of function correlated LSD1 binding proteins are provided, and we tried to figure out the role of LSD1 in different cancer types, including hematological malignancies and solid tumors. A critical description of mutation preference for LSD1 in different tumors was also discussed. Recent research findings clearly showed that the abrogation of LSD1 demethylase activity via LSD1 inhibitors markedly reduced the growth of cancer cells. But there are still many ambiguities regarding the role of LSD1 in different cancers. Therefore, targeting LSD1 for treating different cancers is still reductionist, and many challenges need to be met to improve the therapeutic outcomes of LSD1 inhibitors.

Keywords: Cancer; EMT; Epigenetics; Histone demethylase; LSD1; Leukemia.

Publication types

Review

MeSH terms

Carcinogenesis
Histone Demethylases*
Humans
Neoplasms* / drug therapy

Substances

Histone Demethylases
KDM1A protein, human