NLRP3 and cancer: Pathogenesis and therapeutic opportunities

Pharmacol Ther. 2023 Nov:251:108545. doi: 10.1016/j.pharmthera.2023.108545. Epub 2023 Oct 21.

Abstract

More than a decade ago IL-1 blockade was suggested as an add-on therapy for the treatment of cancer. This proposal was based on the overall safety record of anti-IL-1 biologics and the anti-tumor properties of IL-1 blockade in animal models of cancer. Today, a new frontier in IL-1 activity regulation has developed with several orally active NLRP3 inhibitors currently in clinical trials, including cancer. Despite an increasing body of evidence suggesting a role of NLRP3 and IL-1-mediated inflammation driving cancer initiation, immunosuppression, growth, and metastasis, NLRP3 activation in cancer remains controversial. In this review, we discuss the recent advances in the understanding of NLRP3 activation in cancer. Further, we discuss the current opportunities for NLRP3 inhibition in cancer intervention with novel small molecules.

Keywords: Caspase-1; IL-1 family; NLRP3; Pyroptosis; Response to therapy; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Inflammasomes
  • Inflammation / drug therapy
  • Interleukin-1
  • NLR Family, Pyrin Domain-Containing 3 Protein* / physiology
  • Neoplasms* / drug therapy
  • Reactive Oxygen Species

Substances

  • Inflammasomes
  • Interleukin-1
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • NLRP3 protein, human