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Olaparib is effective in combination with, and as maintenance therapy after, first-line endocrine therapy in prostate cancer cells.
Feiersinger, Gertrud E; Trattnig, Kristina; Leitner, Peter D; Guggenberger, Fabian; Oberhuber, Alexander; Peer, Sarah; Hermann, Martin; Skvortsova, Ira; Vrbkova, Jana; Bouchal, Jan; Culig, Zoran; Santer, Frédéric R.
Afiliación
  • Feiersinger GE; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Trattnig K; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Leitner PD; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Guggenberger F; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Oberhuber A; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Peer S; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Hermann M; Department of Anaesthesia and Intensive Care, Medical University of Innsbruck, Austria.
  • Skvortsova I; Department of Radiotherapy and Radiation Oncology, Medical University of Innsbruck, Austria.
  • Vrbkova J; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
  • Bouchal J; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
  • Culig Z; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
  • Santer FR; Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Austria.
Mol Oncol ; 12(4): 561-576, 2018 04.
Article en En | MEDLINE | ID: mdl-29465803
A number of prostate cancer (PCa)-specific genomic aberrations (denominated BRCAness genes) have been discovered implicating sensitivity to PARP inhibition within the concept of synthetic lethality. Recent clinical studies show favorable results for the PARP inhibitor olaparib used as single agent for treatment of metastatic castration-resistant PCa. Using 2D and 3D cell culture models mimicking the different treatment and progression stages of PCa, we evaluated a potential use for olaparib in combination with first-line endocrine treatments, androgen deprivation, and complete androgen blockade, and as a maintenance therapy following on from endocrine therapy. We demonstrate that the LNCaP cell line, possessing multiple aberrations in BRCAness genes, is sensitive to olaparib. Additive effects of olaparib combined with endocrine treatments in LNCaP are noted. In contrast, we find that the TMPRSS2:ERG fusion-positive cell lines VCaP and DuCaP do not show signs of synthetic lethality, but are sensitive to cytotoxic effects caused by olaparib. In consequence, additive effects of olaparib with endocrine therapy were not observable in these cell lines, showing the need for synthetic lethality in combination treatment regimens. Additionally, we show that PCa cells remain sensitive to olaparib treatment after initial androgen deprivation implicating a possible use of olaparib as maintenance therapy. In sum, our preclinical data recommend olaparib as a synthetic lethal treatment option in combination or sequenced to first-line endocrine therapy for PCa patients with diagnosed BRCAness.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ftalazinas / Piperazinas / Quimioterapia de Mantención / Neoplasias de la Próstata Resistentes a la Castración / Andrógenos / Modelos Biológicos Límite: Humans / Male Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ftalazinas / Piperazinas / Quimioterapia de Mantención / Neoplasias de la Próstata Resistentes a la Castración / Andrógenos / Modelos Biológicos Límite: Humans / Male Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos