Advances in targeting the WNT/β-catenin signaling pathway in cancer

Avradip Chatterjee; Sayan Paul; Bharti Bisht; Shelley Bhattacharya; Sudhakar Sivasubramaniam; Manash K Paul

doi:10.1016/j.drudis.2021.07.007

Advances in targeting the WNT/β-catenin signaling pathway in cancer

Drug Discov Today. 2022 Jan;27(1):82-101. doi: 10.1016/j.drudis.2021.07.007. Epub 2021 Jul 10.

Authors

Avradip Chatterjee¹, Sayan Paul², Bharti Bisht³, Shelley Bhattacharya⁴, Sudhakar Sivasubramaniam⁵, Manash K Paul⁶

Affiliations

¹ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² Department of Biotechnology, Manonmaniam Sundaranar University, Tirunelveli, Tamil Nadu 627012, India; Centre for Cardiovascular Biology and Disease, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore 560065, India.
³ Department of Thoracic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
⁴ Environmental Toxicology Laboratory, Department of Zoology (Centre for Advanced Studies), Visva Bharati (A Central University), Santiniketan 731235, India.
⁵ Department of Biotechnology, Manonmaniam Sundaranar University, Tirunelveli, Tamil Nadu 627012, India.
⁶ Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address: manashp@ucla.edu.

PMID: 34252612
DOI: 10.1016/j.drudis.2021.07.007

Abstract

WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.

Keywords: Artificial intelligence; Cancer; Challenges; Clinical trials; Drug design; Inhibitors; Natural products; Nuclear transport; Phase transition; Phosphorylation; Protein-small molecule interaction; Targeting protein-protein interaction; WNT/β-catenin signaling.

Publication types

Review

MeSH terms

Biological Products / pharmacology*
Drug Design
Humans
Molecular Targeted Therapy* / methods
Molecular Targeted Therapy* / trends
Neoplasms* / drug therapy
Neoplasms* / metabolism
Wnt Signaling Pathway* / drug effects
Wnt Signaling Pathway* / physiology

Substances

Biological Products