NLRP3 and cancer: Pathogenesis and therapeutic opportunities

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacology & Therapeutics Pub Date : 2023-11-01 DOI:10.1016/j.pharmthera.2023.108545
Isak W. Tengesdal, Charles A. Dinarello, Carlo Marchetti
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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.

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NLRP3和癌症:发病机制和治疗机会。
十多年前,IL-1阻断被建议作为治疗癌症的附加疗法。该建议基于抗IL-1生物制品的总体安全性记录以及IL-1阻断剂在癌症动物模型中的抗肿瘤特性。今天,包括癌症在内的几种口服活性NLRP3抑制剂已开发出IL-1活性调节的新前沿。尽管越来越多的证据表明NLRP3和IL-1介导的炎症在驱动癌症发生、免疫抑制、生长和转移中的作用,但NLRP3在癌症中的激活仍然存在争议。在这篇综述中,我们讨论了在理解癌症中NLRP3激活的最新进展。此外,我们还讨论了新型小分子在癌症干预中抑制NLRP3的当前机会。
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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
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