Academic Journal
EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer
| Τίτλος: | EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer |
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| Συγγραφείς: | Rose, Michael, Maurer, Angela, Wirtz, Julia, Bleilevens, Andreas, Waldmann, Tanja, Wenz, Maximilian, Eyll, Marie, Geelvink, Mirja, Gereitzig, Melanie, Rüchel, Nadine, Denecke, Bernd, Eltze, Elke, Herrmann, Edwin, Toma, Marieta, Horst, David, Grimm, Tobias, Denzinger, Stefan, Ecke, Thorsten, Vögeli, Thomas Alexander, Knuechel, Ruth, Maurer, Jochen, Gaisa, Nadine |
| Πηγή: | http://lobid.org/resources/99370678536806441#!, 39(44):6856-6870. |
| Έτος έκδοσης: | 2020 |
| Συλλογή: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| Θεματικοί όροι: | Bladder cancer, Gene Expression Regulation, Neoplastic [MeSH], Urinary Bladder/pathology [MeSH], Cell Line, Tumor [MeSH], Aged [MeSH], Receptor, ErbB-2/metabolism [MeSH], Drug Synergism [MeSH], Urinary Bladder Neoplasms/drug therapy [MeSH], Cohort Studies [MeSH], Carcinoma, Transitional Cell/pathology [MeSH], ErbB Receptors/metabolism [MeSH], Transitional Cell/genetics [MeSH], Male [MeSH], Transitional Cell/drug therapy [MeSH], ErbB-2/antagonists, Gefitinib/therapeutic use [MeSH], Signal Transduction/drug effects [MeSH], Urinary Bladder Neoplasms/genetics [MeSH], ErbB-4/metabolism [MeSH], Squamous Cell/pathology [MeSH], Female [MeSH], Drug Resistance, Neoplasm/drug effects [MeSH], Protein Kinase Inhibitors/pharmacology [MeSH], ErbB Receptors/antagonists, Humans [MeSH] |
| Περιγραφή: | 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 activating EGFR mutations. 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. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| Relation: | https://repository.publisso.de/resource/frl:6471340; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605436/ |
| DOI: | 10.1038/s41388-020-01465-y |
| Διαθεσιμότητα: | https://repository.publisso.de/resource/frl:6471340 https://doi.org/10.1038/s41388-020-01465-y https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605436/ |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Αριθμός Καταχώρησης: | edsbas.D77725C9 |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1038/s41388-020-01465-y |
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