Development of targeted therapy of NRF2high esophageal squamous cell carcinoma

Chorlada Paiboonrungruang; Emily Simpson; Zhaohui Xiong; Caizhi Huang; Jianying Li; Yahui Li; Xiaoxin Chen

doi:10.1016/j.cellsig.2021.110105

Development of targeted therapy of NRF2^high esophageal squamous cell carcinoma

Cell Signal. 2021 Oct:86:110105. doi: 10.1016/j.cellsig.2021.110105. Epub 2021 Aug 4.

Authors

Chorlada Paiboonrungruang¹, Emily Simpson¹, Zhaohui Xiong¹, Caizhi Huang², Jianying Li³, Yahui Li¹, Xiaoxin Chen⁴

Affiliations

¹ Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA.
² Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27607, USA.
³ Euclados Bioinformatics Solutions, Cary, NC 27519, USA.
⁴ Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: lchen@nccu.edu.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a deadly disease and one of the most aggressive cancers of the gastrointestinal tract. As a master transcription factor regulating the stress response, NRF2 is often mutated and becomes hyperactive, and thus causes chemo-radioresistance and poor survival in human ESCC. There is a great need to develop NRF2 inhibitors for targeted therapy of NRF2^high ESCC. In this review, we mainly focus on three aspects, NRF2 inhibitors and their mechanisms of action, screening novel drug targets, and evaluation of NRF2 activity in the esophagus. A research strategy has been proposed to develop NRF2 inhibitors using human ESCC cells and mouse models.

Keywords: Esophageal squamous cell carcinoma; NRF2.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Cell Line, Tumor
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / drug therapy
Esophageal Squamous Cell Carcinoma* / pathology
Mice
NF-E2-Related Factor 2

Substances

NF-E2-Related Factor 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding