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Status: Bibliographieeintrag

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Verfasst von:Schneider, Meike [VerfasserIn]   i
 Korzeniewski, Nina [VerfasserIn]   i
 Merkle, Konstanze [VerfasserIn]   i
 Schuler, Julia [VerfasserIn]   i
 Grüllich, Carsten [VerfasserIn]   i
 Hadaschik, Boris [VerfasserIn]   i
 Hohenfellner, Markus [VerfasserIn]   i
 Duensing, Stefan [VerfasserIn]   i
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

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