Pharmacological significance of the non-canonical NF-κB pathway in tumorigenesis

Dhakshayini Morgan; Manoj Garg; Vinay Tergaonkar; Soo Yong Tan; Gautam Sethi

doi:10.1016/j.bbcan.2020.188449

Pharmacological significance of the non-canonical NF-κB pathway in tumorigenesis

Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188449. doi: 10.1016/j.bbcan.2020.188449. Epub 2020 Oct 12.

Authors

Dhakshayini Morgan¹, Manoj Garg², Vinay Tergaonkar³, Soo Yong Tan⁴, Gautam Sethi⁵

Affiliations

¹ Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore; Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119 074, Singapore.
² Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Uttar Pradesh, Noida 201313, India.
³ Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore; Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119 074, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address: vinayt@imcb.a-star.edu.sg.
⁴ Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119 074, Singapore; Advanced Molecular Pathology Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Dr, 138673, Singapore.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117 600, Singapore. Electronic address: phcgs@nus.edu.sg.

PMID: 33058996
DOI: 10.1016/j.bbcan.2020.188449

Abstract

The understanding of the impact of the non-canonical NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in several human diseases including autoimmune, inflammatory and cancers has been on the rise. This pathway induces the expression of several important genes involved in diverse biological processes. Though progress has been made in understanding the activation, regulation and biological functions of the non-canonical NF-κB signaling mechanism, no specific drug has been approved to target NF-κB inducing kinase (NIK), the key signaling molecule in this pathway. The inhibition of NIK can serve as a potential therapeutic strategy for various ailments, especially for the treatment of different types of human cancers. There are other targetable downstream molecules in this pathway as well. This review highlights the possible role of the non-canonical NF-κB pathway in normal physiology as well as in different cancers and discusses about various pharmacological strategies to modulate the activation of this pathway.

Keywords: Cancer; Immune system; Inflammation; NF-κB; NIK; Non-canonical; Pharmacological interventions.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Carcinogenesis / drug effects
Carcinogenesis / metabolism*
Gene Expression Regulation, Neoplastic / drug effects
Humans
NF-kappa B / metabolism*
NF-kappaB-Inducing Kinase
Protein Serine-Threonine Kinases / metabolism
Signal Transduction / drug effects

Substances

Antineoplastic Agents
NF-kappa B
Protein Serine-Threonine Kinases