Linoleic Acid Potentiates Response to Chemotherapy in Biliary Tract Cancer Through RARγ Activation
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Le résumé fourni par la source
ABSTRACT Biliary tract cancer (BTC) remains highly challenging owing to its poor prognosis. Although gemcitabine plus cisplatin (Gem/Cis) represents a standard chemotherapy option, treatment resistance significantly limits the outcomes. Metabolic reprogramming influences therapeutic response; however, the specific metabolic determinants of chemosensitivity in BTC are poorly defined. Using untargeted metabolomics followed by targeted validation, we found that plasma linoleic acid (LA) levels were significantly elevated in patients with chemotherapy‐responsive BTC. LA supplementation led to tumor accumulation and synergistically enhanced Gem/Cis‐induced cytotoxicity in vitro and in vivo. Mechanistic investigations revealed that LA activated retinoic acid receptor gamma (RARγ), and pharmacological or genetic ablation of RARγ abolished the chemosensitizing effects of LA, establishing RARγ as an important mediator. Activation of the LA‐RARγ axis orchestrated a dual proapoptotic and pro‐immune transcriptional program. This resulted in increased cancer cell apoptosis and a remodeled immune microenvironment, characterized by reduced PD‐L1 expression and enhanced CD8 + T cell activation. Taken together, this study identified LA as a novel metabolic modulator that potentiates chemotherapy response in BTC through RARγ activation, orchestrating a dual antitumor response by promoting cancer cell apoptosis and enhancing antitumor immunity.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Linoleic Acid Potentiates Response to Chemotherapy in Biliary Tract Cancer Through <scp>RARγ</scp> Activation
- Date Crossref
- 13/11/2025
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Zhejiang Cancer Hospital Department of Hepato‐Pancreato‐Biliary and Gastric Medical Oncology pays non établi dans la noticeÉtablissement de santé
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Zhejiang Academy of Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang Hospital Department of Oncology pays non établi dans la noticeÉtablissement de santé
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Ningbo University Affiliated Hospital Department of Gastroenterology pays non établi dans la noticeÉtablissement de santé
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Ningbo First Hospital pays non établi dans la noticeÉtablissement de santé
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Hangzhou Xixi hospital Department of Oncology pays non établi dans la noticeÉtablissement de santé
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Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province Hangzhou China pays non établi dans la noticeStructure de recherche
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the First Affiliated Hospital of Ningbo University Ningbo China Department of Gastroenterology pays non établi dans la noticeUniversité ou école supérieure
Department of Hepato‐Pancreato‐Biliary and Gastric Medical Oncology — Zhejiang Cancer Hospital, Zhejiang Academy of Medical Sciences et Department of Oncology — Zhejiang Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.