NOD-like receptor signaling in inflammation-associated cancers: From functions to targeted therapies

Abstract

Background: Recently, many studies have reported that some botanicals and natural products were able to regulate NOD-like receptor signaling. NOD-like receptors (NLRs) have been established as crucial regulators in inflammation-associated tumorigenesis, angiogenesis, cancer cell stemness and chemoresistance. NLRs specifically sense pathogen-associated molecular patterns and respond by activating other signaling regulators, including Rip2 kinase, NF-κB, MAPK and ASC/caspase-1, leading to the secretion of various cytokines.

Purpose: The aim of this article is to review the molecular mechanisms of NOD-like receptor signaling in inflammation-associated cancers and the NLRs-targeted botanicals and synthetic small molecules in cancer intervention.

Results: Aberrant activation of NLRs occurs in various cancers, orchestrating the tissue microenvironment and potentiating neoplastic risk. Blocking NLR inflammasome activation by botanicals or synthetic small molecules may be a valuable way to prevent cancer progression. Moreover, due to the roles of NLRs in regulating cytokine production, NLR signaling may be correlated with senescence-associated secretory phenotype.

Conclusion: In this review, we discuss how NLR signaling is involved in inflammation-associated cancers, and highlight the NLR-targeted botanicals and synthetic small molecules in cancer intervention.

Keywords: Botanicals; Cancer stem cell; Chemoresistance; Inflammation-associated cancer; NOD-like receptors; Senescence-associated secretory phenotype.