Targeting NF-κB Signaling in Cancer Stem Cells: A Narrative Review

Autor: Barbara Kaltschmidt, Kaya E. Witte, Johannes F. W. Greiner, Florian Weissinger, Christian Kaltschmidt
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biomedicines, Vol 10, Iss 2, p 261 (2022)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines10020261
Popis: Among the cell populations existing within a tumor, cancer stem cells are responsible for metastasis formation and chemotherapeutic resistance. In the present review, we focus on the transcription factor NF-κB, which is present in every cell type including cancer stem cells. NF-κB is involved in pro-tumor inflammation by its target gene interleukin 1 (IL1) and can be activated by a feed-forward loop in an IL1-dependent manner. Here, we summarize current strategies targeting NF-κB by chemicals and biologicals within an integrated cancer therapy. Specifically, we start with a tyrosine kinase inhibitor targeting epidermal growth factor (EGF)-receptor-mediated phosphorylation. Furthermore, we summarize current strategies of multiple myeloma treatment involving lenalidomide, bortezomib, and dexamethasone as potential NF-κB inhibitors. Finally, we discuss programmed death-ligand 1 (PD-L1) as an NF-κB target gene and its role in checkpoint therapy. We conclude, that NF-κB inhibition by specific inhibitors of IκB kinase was of no clinical use but inhibition of upstream and downstream targets with drugs or biologicals might be a fruitful way to treat cancer stem cells.
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