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Journal of Cancer Research and Clinical Oncology

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01.04.2012 | Original Article

Combination of a MDR1-targeted replicative adenovirus and chemotherapy for the therapy of pretreated ovarian cancer

verfasst von: Daniel T. Rein, Anne Volkmer, Gerd Bauerschmitz, Ines M. Beyer, Wolfgang Janni, Markus C. Fleisch, Anne Kathrin Welter, Dirk Bauerschlag, Thomas Schöndorf, Martina Breidenbach

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2012

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Abstract

Purpose

Targeted oncolytic adenoviruses capable of replication selectively in cancer cells are an appealing approach for the treatment of various cancer types refractory to conventional therapies. The aim of this study was to evaluate the effect of Ad5/3MDR1E1, a multidrug resistance gene 1 (MDR1)-targeted fiber-modified replication-competent adenovirus for the therapy of platinum-pretreated ovarian cancer in combination with cytostatic agents.

Methods

MDR1-specific tumor cell killing of Ad5/3MDR1E1 was systematically evaluated in chemotherapy naïve and pretreated ovarian cancer cells in vitro. Combinations of Ad5/3MDR1E1 and cytostatic agents were studied in vivo and in vitro. An in vivo hepatotoxicity model was used to evaluate liver toxicity.

Results

We demonstrate efficient oncolysis of Ad5/3MDR1E1 in chemotherapy-resistant ovarian cancer cells as well as therapeutic efficacy in an orthotopic mouse model. Further, combining Ad5/3MDR1E1 with paclitaxel resulted in greater therapeutic benefit than either agent alone.

Conclusion

These preclinical data suggest that a fiber-modified adenovirus vector under the control of the MDR1 promoter represents a promising treatment strategy for platinum-pretreated ovarian cancer as a single agent or in combination with conventional anticancer drugs.

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Titel: Combination of a MDR1-targeted replicative adenovirus and chemotherapy for the therapy of pretreated ovarian cancer
verfasst von: Daniel T. Rein
Anne Volkmer
Gerd Bauerschmitz
Ines M. Beyer
Wolfgang Janni
Markus C. Fleisch
Anne Kathrin Welter
Dirk Bauerschlag
Thomas Schöndorf
Martina Breidenbach
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1135-5

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Combination of a MDR1-targeted replicative adenovirus and chemotherapy for the therapy of pretreated ovarian cancer

Abstract

Purpose

Methods

Results

Conclusion

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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