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| Item Type: | Preprint |
|---|---|
| Title: | Esophageal adenocarcinoma relapse after chemoradiation is dominated by a basal-like subtype |
| Creators Name: | Hoppe, S., Noseir, S., Yazbeck, A., Zaburannyi, N., Grossbach, J., Lyu, S.I., Velazquez Camacho, O., Müller, S., Gebauer, F., Richartz, V., Holz, B., Berg, J., Achter, V., Altmüller, J., Becker, K., Arolt, C., Meder, L., Zhao, Y., Schlößer, H., Baus, W.W., Kamp, F., Baues, C., Beyer, A., Odenthal, M., Quaas, A., Buettner, R. and Hillmer, A.M. |
| Abstract: | Neoadjuvant chemoradiation therapy (RCT) is a frequently used treatment regimen for esophageal adenocarcinoma (EAC); however, the response varies dramatically, and resistance is a clinical challenge. We aimed to identify the molecular mechanisms underlying RCT resistance. We established a mouse xenograft RCT model with human EAC cell lines representing different response groups, and tested enhanced genomic instability as a potential evolutionary modulator by reducing BRCA2 function. Xenografts that relapsed after RCT displayed upregulation of stress response keratins, including KRT6 and KRT16 connected with a basal-like transcriptomic/ proteomic phenotype. We screened our cohort of 728 patients with EAC and found significantly shorter overall survival for patients with KRT6-high tumors, driven by patients receiving neoadjuvant treatment. Overall, we identified a basal-like cell state in EAC that reflects RCT relapse. The basal-like subtype is a marker of treatment failure, providing a new avenue for translational research to overcome RCT resistance. |
| Keywords: | Esophageal Adenocarcinoma, Chemoradiation Therapy, Resistance, Adaptation, Tumor Evolution, Basal-Like, Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.01.28.635332 |
| Date: | 1 February 2025 |
| Official Publication: | https://doi.org/10.1101/2025.01.28.635332 |
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