The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights
Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-ass...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268124005556 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586274396962816 |
|---|---|
| author | Valentina Arrè Roberto Negro Gianluigi Giannelli |
| author_facet | Valentina Arrè Roberto Negro Gianluigi Giannelli |
| author_sort | Valentina Arrè |
| collection | DOAJ |
| description | Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC. Among others, the inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 3 (NLRP3), and absent in melanoma 2 (AIM2), exhibit a dual role in HCC background. It has been reported that they can exert oncosuppressive functions by triggering the inflammatory death of cancer cells. Vice versa, chronic activation contributes to the development of a pro-tumorigenic environment, thus supporting tumor growth. In addition, other inflammasomes such as Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 6 and 12 (NLRP6 and NLRP12, respectively) regulate HCC onset and progression, although more experimental evidence is required. This review focuses on the molecular mechanisms underpinning the inflammasome's contribution to the onset, progression and spread of HCC. Moreover, we will explore the potential therapeutic approaches currently under investigation, which aim to improve the efficacy and reduce the side effects of the treatments currently available. Targeting inflammasomes may be a promising therapeutic strategy for the treatment of HCC, offering new opportunities to improve patient prognosis. |
| format | Article |
| id | doaj-art-80243eddd87d4bbea06d22509826694f |
| institution | Kabale University |
| issn | 1665-2681 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj-art-80243eddd87d4bbea06d22509826694f2025-01-26T05:03:38ZengElsevierAnnals of Hepatology1665-26812025-01-01301101772The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insightsValentina Arrè0Roberto Negro1Gianluigi Giannelli2Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; Corresponding authors.Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, ItalyScientific Direction, National Institute of Gastroenterology, “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; Corresponding authors.Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC. Among others, the inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 3 (NLRP3), and absent in melanoma 2 (AIM2), exhibit a dual role in HCC background. It has been reported that they can exert oncosuppressive functions by triggering the inflammatory death of cancer cells. Vice versa, chronic activation contributes to the development of a pro-tumorigenic environment, thus supporting tumor growth. In addition, other inflammasomes such as Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 6 and 12 (NLRP6 and NLRP12, respectively) regulate HCC onset and progression, although more experimental evidence is required. This review focuses on the molecular mechanisms underpinning the inflammasome's contribution to the onset, progression and spread of HCC. Moreover, we will explore the potential therapeutic approaches currently under investigation, which aim to improve the efficacy and reduce the side effects of the treatments currently available. Targeting inflammasomes may be a promising therapeutic strategy for the treatment of HCC, offering new opportunities to improve patient prognosis.http://www.sciencedirect.com/science/article/pii/S1665268124005556Hepatocellular carcinomaInflammasomeNLRP3AIM2Therapeutic approach |
| spellingShingle | Valentina Arrè Roberto Negro Gianluigi Giannelli The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights Annals of Hepatology Hepatocellular carcinoma Inflammasome NLRP3 AIM2 Therapeutic approach |
| title | The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights |
| title_full | The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights |
| title_fullStr | The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights |
| title_full_unstemmed | The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights |
| title_short | The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights |
| title_sort | role of inflammasomes in hepatocellular carcinoma mechanisms and therapeutic insights |
| topic | Hepatocellular carcinoma Inflammasome NLRP3 AIM2 Therapeutic approach |
| url | http://www.sciencedirect.com/science/article/pii/S1665268124005556 |
| work_keys_str_mv | AT valentinaarre theroleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights AT robertonegro theroleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights AT gianluigigiannelli theroleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights AT valentinaarre roleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights AT robertonegro roleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights AT gianluigigiannelli roleofinflammasomesinhepatocellularcarcinomamechanismsandtherapeuticinsights |