ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCombination Therapies in Cancer Treatment: Enhancing Efficacy and Reducing ResistanceView all 19 articles
Activation of the STING pathway potentiates the antitumor efficacy of doxorubicin in soft-tissue sarcoma
Provisionally accepted
- National Cancer Center, Goyang-si, Republic of Korea
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Background Systemic treatment of soft-tissue sarcoma (STS) relies on cytotoxic chemotherapy, with doxorubicin being the key therapeutic agent. However, immune activation is required for optimal antitumor effects of doxorubicin. This study investigated whether activation of the STING pathway enhances doxorubicin's antitumor effect in STS. Methods STS cell lines were treated with doxorubicin to evaluate the activation of STING pathway. Deletion of Sting1 gene was employed to validate its role in mediating doxorubicin's effects. In a syngeneic mouse model of STS, doxorubicin was administered alone or in combination with a STING agonist ADU-S100. Tumor-infiltrating CD45+ cells were magnetically sorted for RNA sequencing to identify genes and pathways linked to STING activation. The upregulated genes were analyzed for their association with survival in the Cancer Genome Atlas Sarcoma (TCGA-SARC) patient cohort. Results Doxorubicin induced cytosolic DNA leakage in STS cell lines, triggering the activation of STING pathway. Deletion of Sting1 attenuated doxorubicin-induced upregulation of proinflammatory cytokines in cells. In the syngeneic mouse model of STS, doxorubicin suppressed tumor growth, an effect significantly enhanced by
Keywords: Soft-tissue sarcoma, STING pathway, immunostimulation, chemotherapy, Doxorubicin
Received: 24 May 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Choi, Lee and Kong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wonyoung Choi
Sun-Young Kong
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