STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy

Abstract As cancer continues to rank among the leading causes of death, the demand for novel treatments has never been higher. Immunotherapy shows promise, yet many solid tumors such as pancreatic cancer or glioblastoma remain resistant. In these, the “cold” tumor microenvironment with low immune ce...

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Main Authors: Laura Gehrcken, Christophe Deben, Evelien Smits, Jonas R.M. Van Audenaerde
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202500296
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author Laura Gehrcken
Christophe Deben
Evelien Smits
Jonas R.M. Van Audenaerde
author_facet Laura Gehrcken
Christophe Deben
Evelien Smits
Jonas R.M. Van Audenaerde
author_sort Laura Gehrcken
collection DOAJ
description Abstract As cancer continues to rank among the leading causes of death, the demand for novel treatments has never been higher. Immunotherapy shows promise, yet many solid tumors such as pancreatic cancer or glioblastoma remain resistant. In these, the “cold” tumor microenvironment with low immune cell infiltration and inactive anti‐tumoral immune cells leads to increased tumor resistance to these drugs. This resistance has driven the development of several drug candidates, including stimulators of interferon genes (STING) agonists to reprogram the immune system to fight off tumors. Preclinical studies demonstrated that STING agonists can trigger the cancer immunity cycle and increase type I interferon secretion and T cell activation, which subsequently induces tumor regression. Despite promising preclinical data, biological and physical challenges persist in translating the success of STING agonists into clinical trials. Nonetheless, novel combination strategies are emerging, investigating the combination of these agonists with other immunotherapies, presenting encouraging preclinical results. This review will examine these potential combination strategies for STING agonists and assess the benefits and challenges of employing them in cancer immunotherapy.
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spelling doaj-art-d0793b8b8dc54cb08b2b3bad74ecea532025-08-20T03:48:47ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202500296STING Agonists and How to Reach Their Full Potential in Cancer ImmunotherapyLaura Gehrcken0Christophe Deben1Evelien Smits2Jonas R.M. Van Audenaerde3Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences University of Antwerp Wilrijk 2610 BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences University of Antwerp Wilrijk 2610 BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences University of Antwerp Wilrijk 2610 BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences University of Antwerp Wilrijk 2610 BelgiumAbstract As cancer continues to rank among the leading causes of death, the demand for novel treatments has never been higher. Immunotherapy shows promise, yet many solid tumors such as pancreatic cancer or glioblastoma remain resistant. In these, the “cold” tumor microenvironment with low immune cell infiltration and inactive anti‐tumoral immune cells leads to increased tumor resistance to these drugs. This resistance has driven the development of several drug candidates, including stimulators of interferon genes (STING) agonists to reprogram the immune system to fight off tumors. Preclinical studies demonstrated that STING agonists can trigger the cancer immunity cycle and increase type I interferon secretion and T cell activation, which subsequently induces tumor regression. Despite promising preclinical data, biological and physical challenges persist in translating the success of STING agonists into clinical trials. Nonetheless, novel combination strategies are emerging, investigating the combination of these agonists with other immunotherapies, presenting encouraging preclinical results. This review will examine these potential combination strategies for STING agonists and assess the benefits and challenges of employing them in cancer immunotherapy.https://doi.org/10.1002/advs.202500296cancerimmunotherapySTING agoniststumor microenvironmenttumor resistance
spellingShingle Laura Gehrcken
Christophe Deben
Evelien Smits
Jonas R.M. Van Audenaerde
STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
Advanced Science
cancer
immunotherapy
STING agonists
tumor microenvironment
tumor resistance
title STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
title_full STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
title_fullStr STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
title_full_unstemmed STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
title_short STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
title_sort sting agonists and how to reach their full potential in cancer immunotherapy
topic cancer
immunotherapy
STING agonists
tumor microenvironment
tumor resistance
url https://doi.org/10.1002/advs.202500296
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