The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers

Gouravani, Mahdi; Khalili, Nastaran; Razi, Sepideh; Keshavarz-Fathi, Mahsa; Rezaei, Nima

doi:10.1080/1744666x.2020.1713755

Cited by 25 publications

(22 citation statements)

References 142 publications

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“…Since the NLRP3 inflammasome plays an important role not only in hematological diseases but, also, in many inflammatory diseases [88] and cancers [89,90], it has gained special interest as a promising therapeutic target. Therefore, several pharmacological inhibitors of the NLRP3 inflammasome have been developed to intervene at different levels in the complex signaling pathway, as recently summarized [86,91].…”

Section: The Nlrp3 Inflammasome As a Therapeutic Targetmentioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

Urwanisch

Luciano

Horejs‐Hoeck

2021

IJMS

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Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

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Section: The Nlrp3 Inflammasome As a Therapeutic Targetmentioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

Urwanisch

Luciano

Horejs‐Hoeck

2021

IJMS

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“…The MPNs are defined by a chronic inflammatory status contributing to microenvironmental transformation necessary for supporting tumor progression and severity of the disease [4]. inflammation plays an important and defined role in cancer development affecting all tumorigenesis stage, including initiation, promotion, malignant conversion, invasion and metastasis [5]. Indeed, cancer-related inflammation is triggered by a series of signals from immune system cells such as macrophages, dendritic cells (DCs), NK cells (natural killer), neutrophils and T and B lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Longhitano

Volti

Giallongo

et al. 2020

JCM

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Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are rare hematological conditions known as myeloproliferative neoplasms (MPNs). They are characterized for being BCR-ABL negative malignancies and affected patients often present with symptoms which can significantly impact their quality of life. MPNs are characterized by a clonal proliferation of an abnormal hematopoietic stem/progenitor cell. In MPNs; cells of all myeloid lineages; including those involved in the immune and inflammatory response; may belong to the malignant clone thus leading to an altered immune response and an overexpression of cytokines and inflammatory receptors; further worsening chronic inflammation. Many of these cytokines; in particular, IL-1β and IL-18; are released in active form by activating the inflammasome complexes which in turn mediate the inflammatory process. Despite this; little is known about the functional effects of stem cell-driven inflammasome signaling in MPN pathogenesis. In this review we focused on the role of inflammatory pathway and inflammasome in MPN diseases. A better understanding of the inflammatory-state-driving MPNs and of the role of the inflammasome may provide new insights on possible therapeutic strategies

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“…For the remaining six genes, five (CASP1, CASP14, RBL1, HNF4A and RALA) had weaker links (e.g. expression linked or pathway membership), but no clear experimental evidence ( Gouravani et al , 2020 ; Krajewska, 2005 ; Schade et al , 2019 ; Seibold et al , 2019 ; Wang et al , 2020 ).…”

Section: Resultsmentioning

confidence: 98%

Prediction of cancer driver genes through network-based moment propagation of mutation scores

et al. 2020

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Motivation Gaining a comprehensive understanding of the genetics underlying cancer development and progression is a central goal of biomedical research. Its accomplishment promises key mechanistic, diagnostic and therapeutic insights. One major step in this direction is the identification of genes that drive the emergence of tumors upon mutation. Recent advances in the field of computational biology have shown the potential of combining genetic summary statistics that represent the mutational burden in genes with biological networks, such as protein–protein interaction networks, to identify cancer driver genes. Those approaches superimpose the summary statistics on the nodes in the network, followed by an unsupervised propagation of the node scores through the network. However, this unsupervised setting does not leverage any knowledge on well-established cancer genes, a potentially valuable resource to improve the identification of novel cancer drivers. Results We develop a novel node embedding that enables classification of cancer driver genes in a supervised setting. The embedding combines a representation of the mutation score distribution in a node’s local neighborhood with network propagation. We leverage the knowledge of well-established cancer driver genes to define a positive class, resulting in a partially labeled dataset, and develop a cross-validation scheme to enable supervised prediction. The proposed node embedding followed by a supervised classification improves the predictive performance compared with baseline methods and yields a set of promising genes that constitute candidates for further biological validation. Availability and implementation Code available at https://github.com/BorgwardtLab/MoProEmbeddings. Supplementary information Supplementary data are available at Bioinformatics online.

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The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers

Cited by 25 publications

References 142 publications

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Prediction of cancer driver genes through network-based moment propagation of mutation scores

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