| Online-Ressource |
Verfasst von: | Schneider, Meike [VerfasserIn]  |
| Korzeniewski, Nina [VerfasserIn]  |
| Merkle, Konstanze [VerfasserIn]  |
| Schuler, Julia [VerfasserIn]  |
| Grüllich, Carsten [VerfasserIn]  |
| Hadaschik, Boris [VerfasserIn]  |
| Hohenfellner, Markus [VerfasserIn]  |
| Duensing, Stefan [VerfasserIn]  |
Titel: | The tyrosine kinase inhibitor nilotinib has antineoplastic activity in prostate cancer cells but up-regulates the ERK survival signal |
Titelzusatz: | implications for targeted therapies |
Verf.angabe: | Meike Schneider, M.D., Nina Korzeniewski, Ph. D., Konstanze Merkle, Julia Schüler, D.V.M., Ph. D., Carsten Grüllich, M.D., Boris Hadaschik, M.D., Markus Hohenfellner, M.D., Stefan Duensing, M.D. |
Jahr: | 2015 |
Jahr des Originals: | 2014 |
Umfang: | 7 S. |
Fussnoten: | Available online 2 July 2014 ; Gesehen am 08.07.2020 |
Titel Quelle: | Enthalten in: Urologic oncology |
Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1995 |
Jahr Quelle: | 2015 |
Band/Heft Quelle: | 33(2015), 2, Seite 72.e1-72.e7 |
ISSN Quelle: | 1873-2496 |
Abstract: | Background: Novel therapeutic options beyond hormone ablation and chemotherapy are urgently needed for patients with advanced prostate cancer. Tyrosine kinase inhibitors (TKIs) are an attractive option as advanced prostate cancers show a highly altered phosphotyrosine proteome. However, despite favorable initial clinical results, the combination of the TKI dasatinib with docetaxel did not result in improved patient survival for reasons that are not known in detail. - Methods: The National Cancer Institute-Approved Oncology Drug Set II was used in a phenotypic drug screen to identify novel compounds with antineoplastic activity in prostate cancer cells. Validation experiments were carried out in vitro and in vivo. - Results: We identified the TKI nilotinib as a novel compound with antineoplastic activity in hormone-refractory prostate cancer cells. However, further analyses revealed that treatment with nilotinib was associated with a significant up-regulation of the phospho-extracellular-signal-regulated kinases (ERK) survival signal. ERK blockade alone led to a significant antitumoral effect and enhanced the cytotoxicity of nilotinib when used in combination. - Conclusions: Our findings underscore that TKIs, such as nilotinib, have antitumoral activity in prostate cancer cells but that survival signals, such as ERK up-regulation, may mitigate their effectiveness. ERK blockade alone or in combination with TKIs may represent a promising therapeutic strategy in advanced prostate cancer. |
DOI: | doi:10.1016/j.urolonc.2014.06.001 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.urolonc.2014.06.001 |
| DOI: https://doi.org/10.1016/j.urolonc.2014.06.001 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Animals |
| Cell Line, Tumor |
| Drug resistance |
| Drug Resistance, Neoplasm |
| ERK |
| Extracellular Signal-Regulated MAP Kinases |
| Humans |
| Male |
| MAP Kinase Signaling System |
| Mice |
| Mice, Mutant Strains |
| Nilotinib |
| Prostate cancer |
| Prostatic Neoplasms |
| Protein Kinase Inhibitors |
| Pyrimidines |
| Random Allocation |
| Translational therapeutics |
| Up-Regulation |
| Xenograft Model Antitumor Assays |
K10plus-PPN: | 171395849X |
Verknüpfungen: | → Zeitschrift |
¬The¬ tyrosine kinase inhibitor nilotinib has antineoplastic activity in prostate cancer cells but up-regulates the ERK survival signal / Schneider, Meike [VerfasserIn]; 2015 (Online-Ressource)