Rose, Michael and Maurer, Angela and Wirtz, Julia and Bleilevens, Andreas and Waldmann, Tanja and Wenz, Maximilian and Eyll, Marie and Geelvink, Mirja and Gereitzig, Melanie and Ruechel, Nadine and Denecke, Bernd and Eltze, Elke and Herrmann, Edwin and Toma, Marieta and Horst, David and Grimm, Tobias and Denzinger, Stefan and Ecke, Thorsten and Voegeli, Thomas Alexander and Knuechel, Ruth and Maurer, Jochen and Gaisa, Nadine T. (2020) EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer. ONCOGENE, 39 (44). pp. 6856-6870. ISSN 0950-9232, 1476-5594
Full text not available from this repository. (Request a copy)Abstract
Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activatingEGFRmutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative "Achilles heel" of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSITIONAL-CELL CARCINOMA; COMPREHENSIVE MOLECULAR CHARACTERIZATION; PHASE-II; LUNG-CANCER; UROTHELIAL CARCINOMA; 1ST-LINE TREATMENT; MASS-ACTION; FAMILY; CHEMOTHERAPY; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2021 09:46 |
| Last Modified: | 11 Mar 2021 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43759 |
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