دورية أكاديمية
FOXO transcriptional activity is associated with response to chemoradiation in EAC
| العنوان: | FOXO transcriptional activity is associated with response to chemoradiation in EAC |
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| المؤلفون: | Creemers, A., van der Zalm, A. P., van de Stolpe, A., Holtzer, L., Stoffels, M., Hooijer, G. K. J., Ebbing, E. A., van Ooijen, H., van Brussel, A. G. C., Aussems-Custers, E. M. G., van Berge Henegouwen, M. I., Hulshof, M. C. C. M., Bergman, J. J. G. H. M., Meijer, S. L., Bijlsma, M. F., van Laarhoven, H. W. M. |
| المصدر: | Creemers , A , van der Zalm , A P , van de Stolpe , A , Holtzer , L , Stoffels , M , Hooijer , G K J , Ebbing , E A , van Ooijen , H , van Brussel , A G C , Aussems-Custers , E M G , van Berge Henegouwen , M I , Hulshof , M C C M , Bergman , J J G H M , Meijer , S L , Bijlsma , M F & van Laarhoven , H W M 2022 , ' FOXO transcriptional activity is .... |
| سنة النشر: | 2022 |
| الوصف: | In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and corresponding recurrence. Activity of six key cancer-related signaling pathways was inferred using the Bayesian inference method. When assessing pre- and post-nCRT samples, lower FOXO transcriptional activity was observed in poor nCRT responders compared to good nCRT responders (p = 0.0017). This poor responder profile was preserved in recurrences compared to matched resections (p = 0.0007). PI3K pathway activity, inversely linked with FOXO activity, was higher in CRT poor responder cell lines compared to CRT good responders. Poor CRT responder cell lines could be sensitized to CRT using PI3K inhibitors. To conclude, by using a novel method to measure signaling pathway activity on clinically available material, we identified an association of low FOXO transcriptional activity with poor response to nCRT. Targeting this pathway sensitized cells for nCRT, underlining its feasibility to select appropriate targeted therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://research.vumc.nl/en/publications/80b93a8d-b56e-435e-acbe-eeb17a7c3f3aTest |
| DOI: | 10.1186/s12967-022-03376-w |
| الإتاحة: | https://doi.org/10.1186/s12967-022-03376-wTest https://research.vumc.nl/en/publications/80b93a8d-b56e-435e-acbe-eeb17a7c3f3aTest http://www.scopus.com/inward/record.url?scp=85128807844&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BCDA877F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12967-022-03376-w |
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