Synergistic effects of imatinib (STI 571) in combination with chemotherapeutic drugs in head and neck cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76855
Title:
Synergistic effects of imatinib (STI 571) in combination with chemotherapeutic drugs in head and neck cancer.
Authors:
Bruce, Iain A; Slevin, Nicholas J ( 0000-0002-3367-7013 ) ; Homer, Jarrod J; McGown, Alan T; Ward, Timothy H
Abstract:
The tyrosine kinase inhibitor imatinib (STI 571; glivec) is a potent inhibitor of bcr-abl, c-kit and platelet-derived growth factor receptors. Imatinib was evaluated both alone and in combination with established chemotherapeutic agents in adenoid cystic carcinoma (ACC) primary cultures and established cell lines representing squamous cell carcinoma of the head and neck (HNSCC). Over 90% of ACC tumors are c-kit-positive, and these primary cultures proved to be of short-term usefulness in assessing chemosensitivity. Interaction was determined over a wide range of drug combinations using a statistical three-dimensional analysis model. Both ACC short-term cultures and HNSCC cell lines were demonstrated to have a response ranging from additive to synergistic when imatinib and cisplatin were combined. The interaction of imatinib on cisplatin-induced DNA cross-linking was further investigated using the comet-X assay. In contrast, significant antagonism was observed when imatinib and gemcitabine were combined. Since gemcitabine is activated by deoxycytidine kinase (dCK), the effect of imatinib on this enzyme was investigated. A dose-dependent inhibition of dCK was observed, highlighting this kinase as a possible additional secondary molecular target for imatinib. This work demonstrates a synergistic interaction between cisplatin and imatinib, which may prove to be clinically relevant in the future management of both ACC and HNSCC.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Citation:
Synergistic effects of imatinib (STI 571) in combination with chemotherapeutic drugs in head and neck cancer. 2005, 16 (7):719-26 Anticancer Drugs
Journal:
Anti-Cancer Drugs
Issue Date:
Aug-2005
URI:
http://hdl.handle.net/10541/76855
PubMed ID:
16027519
Type:
Article
Language:
en
ISSN:
0959-4973
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBruce, Iain A-
dc.contributor.authorSlevin, Nicholas J-
dc.contributor.authorHomer, Jarrod J-
dc.contributor.authorMcGown, Alan T-
dc.contributor.authorWard, Timothy H-
dc.date.accessioned2009-08-10T17:26:53Z-
dc.date.available2009-08-10T17:26:53Z-
dc.date.issued2005-08-
dc.identifier.citationSynergistic effects of imatinib (STI 571) in combination with chemotherapeutic drugs in head and neck cancer. 2005, 16 (7):719-26 Anticancer Drugsen
dc.identifier.issn0959-4973-
dc.identifier.pmid16027519-
dc.identifier.urihttp://hdl.handle.net/10541/76855-
dc.description.abstractThe tyrosine kinase inhibitor imatinib (STI 571; glivec) is a potent inhibitor of bcr-abl, c-kit and platelet-derived growth factor receptors. Imatinib was evaluated both alone and in combination with established chemotherapeutic agents in adenoid cystic carcinoma (ACC) primary cultures and established cell lines representing squamous cell carcinoma of the head and neck (HNSCC). Over 90% of ACC tumors are c-kit-positive, and these primary cultures proved to be of short-term usefulness in assessing chemosensitivity. Interaction was determined over a wide range of drug combinations using a statistical three-dimensional analysis model. Both ACC short-term cultures and HNSCC cell lines were demonstrated to have a response ranging from additive to synergistic when imatinib and cisplatin were combined. The interaction of imatinib on cisplatin-induced DNA cross-linking was further investigated using the comet-X assay. In contrast, significant antagonism was observed when imatinib and gemcitabine were combined. Since gemcitabine is activated by deoxycytidine kinase (dCK), the effect of imatinib on this enzyme was investigated. A dose-dependent inhibition of dCK was observed, highlighting this kinase as a possible additional secondary molecular target for imatinib. This work demonstrates a synergistic interaction between cisplatin and imatinib, which may prove to be clinically relevant in the future management of both ACC and HNSCC.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectHead and Neck Canceren
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarcinoma, Adenoid Cystic-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCell Line, Tumor-
dc.subject.meshComet Assay-
dc.subject.meshDrug Antagonism-
dc.subject.meshDrug Synergism-
dc.subject.meshHead and Neck Neoplasms-
dc.subject.meshHumans-
dc.subject.meshInhibitory Concentration 50-
dc.subject.meshPiperazines-
dc.subject.meshProtein-Tyrosine Kinases-
dc.subject.meshPyrimidines-
dc.titleSynergistic effects of imatinib (STI 571) in combination with chemotherapeutic drugs in head and neck cancer.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalAnti-Cancer Drugsen

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