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Review Open Access

Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review)

  • Authors:
    • Xing Li
    • Lu Chen
    • Ming Zeng
    • Jialun Deng
    • Fan Chen
    • Lingying Yu
    • Mingyue Ao
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Jianyang Chinese Medicine Hospital, Chengdu, Sichuan 641499, P.R. China, Department of Pharmacy, China State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China, Research Center of Traditional Chinese Medicine, Yunnan Research Institute of Traditional Chinese Medicine, Kunming, Yunnan 650051, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 567
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    Published online on: October 2, 2025
       https://doi.org/10.3892/ol.2025.15313
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Abstract

The nuclear factor‑κB (NF‑κB) signaling pathway not only exerts a notable role in inflammation and immune modulation but is also considered a key driver in the initiation and progression of cancer. NF‑κB is closely associated with tumor cell proliferation, differentiation, apoptosis, invasion and metastasis, indicating its notable role in cancer pathogenesis. Based on research into the NF‑κB pathway, the present article studied the biochemical processes involved in the NF‑κB pathway, analyzed potential drug targets and inhibitors and clarified therapeutic strategies for targeting NF‑κB in cancer treatment. The NF‑κB signaling pathway consists of both classical and non‑classical pathways and plays a fundamental role in multiple cancer processes, including cancer cell proliferation, apoptosis, autophagy, inflammation, tumor microenvironment interactions, therapy resistance, ion channel modulation, tumor heterogeneity, and epithelial‑mesenchymal transition (EMT)‑mediated migration, invasion and metastasis. Current therapeutic development has yielded diverse pharmacological agents targeting this pathway, including phytochemical‑derived NF‑κB inhibitors and synthetic molecules for cancer therapy.
View Figures

Figure 1

Simplified diagram of classical and
non-classical NF-κB signaling pathway. NF-κB, nuclear factor-κB,
TNF-α, tumor necrosis factor-α; TNFR, tumor necrosis factor
receptor; IL, interleukin; LPS, lipopolysaccharide; TLR, Toll-like
receptor; IκB, inhibitor of nuclear factor-κB kinase subunit β; P,
phosphate group; RelA, transcription factor p65; BAFF, B-cell
activating factor; BAFFR, B-cell activating factor receptor; CD40L,
CD40 ligand; CD40, tumor necrosis factor receptor superfamily
member 5; RANKL, receptor activator of nuclear factor-κB ligand;
RANK, receptor activator of NF-κB; LTβ, lymphotoxin β; LTβR,
lymphotoxin β receptor; NIK, NF-κB induced kinase; IKKα, inhibitor
of κ kinase α; RelB, transcription factor RelB; p52, 52 kDa
repressor of the inhibitor of the protein kinase.

Figure 2

Tumor cells and biochemical
processes. EMT, epithelial-mesenchymal transition.

Figure 3

NF-κB pathway-related biochemical
processes. NF-κB, nuclear factor-κB; TNF-α, tumor necrosis
factor-α; IL, interleukin; ROS, reactive oxygen species; TLR, Toll
like receptor; TGF, transforming growth factor; RelB, transcription
factor RelB.

Figure 4

Agents and phytochemicals targeting
the NF-κB pathway for cancer treatment. NF-κB, nuclear factor-κB;
IκB, inhibitor of nuclear factor-κB kinase subunit β; TSHG,
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside; VEGF, vascular
endothelial growth factor.
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Copy and paste a formatted citation
Spandidos Publications style
Li X, Chen L, Zeng M, Deng J, Chen F, Yu L and Ao M: Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review). Oncol Lett 30: 567, 2025.
APA
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., & Ao, M. (2025). Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review). Oncology Letters, 30, 567. https://doi.org/10.3892/ol.2025.15313
MLA
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., Ao, M."Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review)". Oncology Letters 30.6 (2025): 567.
Chicago
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., Ao, M."Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review)". Oncology Letters 30, no. 6 (2025): 567. https://doi.org/10.3892/ol.2025.15313
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, Chen L, Zeng M, Deng J, Chen F, Yu L and Ao M: Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review). Oncol Lett 30: 567, 2025.
APA
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., & Ao, M. (2025). Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review). Oncology Letters, 30, 567. https://doi.org/10.3892/ol.2025.15313
MLA
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., Ao, M."Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review)". Oncology Letters 30.6 (2025): 567.
Chicago
Li, X., Chen, L., Zeng, M., Deng, J., Chen, F., Yu, L., Ao, M."Pathogenic role and therapeutic targets of nuclear factor‑κB signaling pathway in cancer (Review)". Oncology Letters 30, no. 6 (2025): 567. https://doi.org/10.3892/ol.2025.15313
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