RNase1-driven ALK-activation is an oncogenic driver and therapeutic target in non-small cell lung cancer
Rattachement africain : cn, us, Éthiopie. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harboring common oncogenic driver mutations such as EGFR, KRAS, and ALK rearrangement. However, ~35-50% of NSCLC patients without tyrosine kinase mutation or rearrangement (non-mutated) cannot benefit from these targeted treatments, highlighting the urgent need for novel therapeutic strategies for this patient population. In this study, we report a non-canonical role of human secretory ribonuclease 1 (RNase1), which binds to and activates wild-type ALK in lung cancer cells, thereby triggering its downstream signaling pathway. RNase1-driven ALK-activation (RDAA) cells exhibit enhanced cell proliferation, migration, and colony formation. Additionally, RDAA facilitates tumor formation in fibroblast models, further underscoring its oncogenic potential in vivo. Importantly, RDAA lung cancer cells exhibit marked sensitivity to FDA-approved ALK inhibitors. Tumor growth suppression and survival were substantially improved in both RDAA-positive NSCLC cell line-derived and patient-derived xenograft tumor models treated with ALK inhibitors. Monoclonal antibodies against RNase1 and phosphorylated-ALK were used to analyze two different human NSCLC tissue cohorts by immunohistochemical staining identified 10.4% (5/48) and 8.5% (100/1173) patients who were RDAA positive, respectively. Notably, among the nine RDAA-positive NSCLC patients who accepted ALK inhibitor treatment, five achieved objective response including two who experienced complete response (CR). Together, the current study identifies RDAA as an oncogenic driver and proposes an effective targeted therapy strategy for non-mutated NSCLC patients.
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 ; titre concordant.
- Titre Crossref
- RNase1-driven ALK-activation is an oncogenic driver and therapeutic target in non-small cell lung cancer
- Date Crossref
- 18/04/2025
- Éditeur
- Springer Science and Business Media LLC
- 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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Sichuan University Department of Medical Oncology pays non établi dans la noticeUniversité ou école supérieure
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West China Hospital of Sichuan University pays non établi dans la noticeÉtablissement de santé
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Sun Yat-sen University Institute of Precision Medicine pays non établi dans la noticeUniversité ou école supérieure
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Harbin Medical University pays non établi dans la noticeUniversité ou école supérieure
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The University of Texas MD Anderson Cancer Center Department of Molecular and Cellular Oncology pays non établi dans la noticeÉtablissement de santé
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Ministry of Education Éthiopie (code pays fourni par la source)Organisme public
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Betta Pharmaceuticals (China) pays non établi dans la noticeEntreprise
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University of Sichuan Department of Thoracic Surgery and Institute of Thoracic Oncology pays non établi dans la noticeUniversité ou école supérieure
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School of Basic Medical Sciences Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion Department of Liver Cancer and Transplant pays non établi dans la noticeUniversité ou école supérieure
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Betta Pharmaceuticals Co. Ltd Hangzhou Repugene Technology Co. pays non établi dans la noticeEntreprise
Department of Medical Oncology — Sichuan University, West China Hospital of Sichuan University et Institute of Precision Medicine — Sun Yat-sen University, avec 8 autres affiliations. Pays d’affiliation : Éthiopie.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.