Standard

FOXO transcriptional activity is associated with response to chemoradiation in EAC. / Creemers, A.; van der Zalm, A. P.; van de Stolpe, A. et al.

In: Journal of translational medicine, Vol. 20, No. 1, 183, 01.12.2022.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Creemers, A, van der Zalm, AP, van de Stolpe, A, Holtzer, L, Stoffels, M, Hooijer, GKJ, Ebbing, EA, van Ooijen, H, van Brussel, AGC, Aussems-Custers, EMG, van Berge Henegouwen, MI, Hulshof, MCCM, Bergman, JJGHM, Meijer, SL, Bijlsma, MF & van Laarhoven, HWM 2022, 'FOXO transcriptional activity is associated with response to chemoradiation in EAC', Journal of translational medicine, vol. 20, no. 1, 183. https://doi.org/10.1186/s12967-022-03376-w

APA

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 associated with response to chemoradiation in EAC. Journal of translational medicine, 20(1), [183]. https://doi.org/10.1186/s12967-022-03376-w

Vancouver

Creemers A, van der Zalm AP, van de Stolpe A, Holtzer L, Stoffels M, Hooijer GKJ et al. FOXO transcriptional activity is associated with response to chemoradiation in EAC. Journal of translational medicine. 2022 Dec 1;20(1):183. doi: 10.1186/s12967-022-03376-w

Author

Creemers, A. ; van der Zalm, A. P. ; van de Stolpe, A. et al. / FOXO transcriptional activity is associated with response to chemoradiation in EAC. In: Journal of translational medicine. 2022 ; Vol. 20, No. 1.

BibTeX

@article{9d13463162944c5dbdfacc9190ffc7db,
title = "FOXO transcriptional activity is associated with response to chemoradiation in EAC",
abstract = "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.",
keywords = "Esophageal adenocarcinoma, Neoadjuvant chemoradiation therapy, Pathway analysis, Predictive",
author = "A. Creemers and {van der Zalm}, {A. P.} and {van de Stolpe}, A. and L. Holtzer and M. Stoffels and Hooijer, {G. K. J.} and Ebbing, {E. A.} and {van Ooijen}, H. and {van Brussel}, {A. G. C.} and Aussems-Custers, {E. M. G.} and {van Berge Henegouwen}, {M. I.} and Hulshof, {M. C. C. M.} and Bergman, {J. J. G. H. M.} and Meijer, {S. L.} and Bijlsma, {M. F.} and {van Laarhoven}, {H. W. M.}",
note = "Funding Information: All authors have read the journal{\textquoteright}s policy on disclosure of potential conflicts of interest. MB has received research funding from Celgene and has acted as a consultant to Servier. HL has served as a consultant for Celgene, BMS, Lilly, and Nordic, and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips and Roche. AS, LH, MS, HO, AB and EAC are employees of Philips. Funding Information: This work was supported by Philips Research and Amsterdam UMC. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "10.1186/s12967-022-03376-w",
language = "English",
volume = "20",
journal = "Journal of translational medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - FOXO transcriptional activity is associated with response to chemoradiation in EAC

AU - Creemers, A.

AU - van der Zalm, A. P.

AU - van de Stolpe, A.

AU - Holtzer, L.

AU - Stoffels, M.

AU - Hooijer, G. K. J.

AU - Ebbing, E. A.

AU - van Ooijen, H.

AU - van Brussel, A. G. C.

AU - Aussems-Custers, E. M. G.

AU - van Berge Henegouwen, M. I.

AU - Hulshof, M. C. C. M.

AU - Bergman, J. J. G. H. M.

AU - Meijer, S. L.

AU - Bijlsma, M. F.

AU - van Laarhoven, H. W. M.

N1 - Funding Information: All authors have read the journal’s policy on disclosure of potential conflicts of interest. MB has received research funding from Celgene and has acted as a consultant to Servier. HL has served as a consultant for Celgene, BMS, Lilly, and Nordic, and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips and Roche. AS, LH, MS, HO, AB and EAC are employees of Philips. Funding Information: This work was supported by Philips Research and Amsterdam UMC. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - 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.

AB - 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.

KW - Esophageal adenocarcinoma

KW - Neoadjuvant chemoradiation therapy

KW - Pathway analysis

KW - Predictive

UR - http://www.scopus.com/inward/record.url?scp=85128807844&partnerID=8YFLogxK

U2 - 10.1186/s12967-022-03376-w

DO - 10.1186/s12967-022-03376-w

M3 - Article

C2 - 35468793

VL - 20

JO - Journal of translational medicine

JF - Journal of translational medicine

SN - 1479-5876

IS - 1

M1 - 183

ER -

ID: 23349005