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NLRP3 and cancer: Pathogenesis and therapeutic opportunities

Isak W Tengesdal1, Charles A Dinarello1, Carlo Marchetti1

  • 1Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.

Pharmacology & Therapeutics
|October 22, 2023
PubMed

Insights

Interleukin-1 (IL-1) blockade shows promise for cancer treatment, with new NLRP3 inhibitors in clinical trials. Understanding NLRP3 activation is key to developing novel cancer therapies.

Area of Science:

  • Immunology
  • Oncology
  • Inflammation Research

Background:

  • Interleukin-1 (IL-1) blockade was proposed over a decade ago as an adjunct cancer therapy, supported by safety data and preclinical anti-tumor effects.
  • Emerging evidence implicates NLRP3 inflammasome activation and IL-1-mediated inflammation in cancer initiation, progression, and metastasis.
  • The precise role of NLRP3 activation in cancer remains a subject of ongoing investigation and debate.

Purpose of the Study:

  • To review recent advancements in understanding NLRP3 inflammasome activation within the context of cancer.
  • To explore the therapeutic potential of targeting NLRP3 for cancer intervention.

Main Methods:

  • Literature review of recent studies on NLRP3 inflammasome and IL-1 in cancer.
  • Analysis of preclinical and clinical data regarding NLRP3 inhibitors in cancer models.
  • Discussion of novel small molecules targeting NLRP3.

Main Results:

  • IL-1 blockade exhibits anti-tumor properties and a favorable safety profile.
  • Several orally active NLRP3 inhibitors are currently in clinical trials for cancer treatment.
  • Controversy exists regarding the exact role of NLRP3 activation in cancer development.

Conclusions:

  • NLRP3 inflammasome and IL-1 signaling are increasingly recognized as critical players in cancer biology.
  • Novel small molecule NLRP3 inhibitors represent a promising therapeutic avenue for cancer intervention.
  • Further research is needed to clarify the complex role of NLRP3 in different cancer types.
Keywords:
Caspase-1IL-1 familyNLRP3PyroptosisResponse to therapyTumor microenvironment

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