دورية أكاديمية

Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer

التفاصيل البيبلوغرافية
العنوان: Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer
المؤلفون: Sanchez-Castillo, Anais, Heylen, Elien, Hounjet, Judith, Savelkouls, Kim G., Lieuwes, Natasja G., Biemans, Rianne, Dubois, Ludwig J., Reynders, Kobe, Rouschop, Kasper M., Vaes, Rianne D. W., De Keersmaecker, Kim, Lambrecht, Maarten, Hendriks, Lizza E. L., De Ruysscher, Dirk K. M., Vooijs, Marc, Kampen, Kim R.
المصدر: Sanchez-Castillo , A , Heylen , E , Hounjet , J , Savelkouls , K G , Lieuwes , N G , Biemans , R , Dubois , L J , Reynders , K , Rouschop , K M , Vaes , R D W , De Keersmaecker , K , Lambrecht , M , Hendriks , L E L , De Ruysscher , D K M , Vooijs , M & Kampen , K R 2024 , ' Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer ' , British Journal of Cancer , vol. 130 ....
سنة النشر: 2024
المجموعة: Maastricht University Research Publications
مصطلحات موضوعية: SERINE HYDROXYMETHYLTRANSFERASE SHMT, PERSISTENT OXIDATIVE STRESS, IONIZING-RADIATION, IN-VIVO, PATHWAY, DNA, PHARMACOKINETICS, MICROENVIRONMENT, IDENTIFICATION, BIOSYNTHESIS
الوصف: BackgroundLung cancer is the most lethal cancer, and 85% of cases are classified as non-small cell lung cancer (NSCLC). Metabolic rewiring is a cancer hallmark that causes treatment resistance, and lacks insights into serine/glycine pathway adaptations upon radiotherapy.MethodsWe analyzed radiotherapy responses using mass-spectrometry-based metabolomics in NSCLC patient's plasma and cell lines. Efficacy of serine/glycine conversion inhibitor sertraline with radiotherapy was investigated by proliferation, clonogenic and spheroid assays, and in vivo using a serine/glycine dependent NSCLC mouse model by assessment of tumor growth, metabolite and cytokine levels, and immune signatures.ResultsSerine/glycine pathway metabolites were significantly consumed in response to radiotherapy in NSCLC patients and cell models. Combining sertraline with radiotherapy impaired NSCLC proliferation, clonogenicity and stem cell self-renewal capacity. In vivo, NSCLC tumor growth was reduced solely in the sertraline plus radiotherapy combination treatment group. Tumor weights linked to systemic serine/glycine pathway metabolite levels, and were inhibited in the combination therapy group. Interestingly, combination therapy reshaped the tumor microenvironment via cytokines associated with natural killer cells, supported by eradication of immune checkpoint galectin-1 and elevated granzyme B levels.ConclusionOur findings highlight that targeting serine/glycine metabolism using sertraline restricts cancer cell recovery from radiotherapy and provides tumor control through immunomodulation in NSCLC.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: https://cris.maastrichtuniversity.nl/en/publications/49054cd1-33dd-4c02-bc97-6da5a34d8bf6Test
DOI: 10.1038/s41416-023-02553-y
الإتاحة: https://doi.org/10.1038/s41416-023-02553-yTest
https://cris.maastrichtuniversity.nl/en/publications/49054cd1-33dd-4c02-bc97-6da5a34d8bf6Test
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.890BF9FB
قاعدة البيانات: BASE