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Jeay, Sebastien; Gaulis, Swann; Ferretti, Stéphane; Albrecht, Geneviève; Barys, Louise; Guthy, Daniel; Halilovic, Ensar; Ito, Moriko; Murakami, Masato; Pornon, Astrid; Ruetz, Stephan; Venkatesan, Kavitha; Yu, Jianjun; Jensen, Michael; Wiesmann, Marion; Wuerthner, Jens; Graus-Porta, Diana

Abstract 2909: A gene signature composed of 13 p53 target genes predicts for response to NVP-CGM097, a novel p53-Mdm2 inhibitor, in cell lines and in human primary tumor xenograft models

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  • Medientyp: E-Artikel
  • Titel: Abstract 2909: A gene signature composed of 13 p53 target genes predicts for response to NVP-CGM097, a novel p53-Mdm2 inhibitor, in cell lines and in human primary tumor xenograft models
  • Beteiligte: Jeay, Sebastien; Gaulis, Swann; Ferretti, Stéphane; Albrecht, Geneviève; Barys, Louise; Guthy, Daniel; Halilovic, Ensar; Ito, Moriko; Murakami, Masato; Pornon, Astrid; Ruetz, Stephan; Venkatesan, Kavitha; Yu, Jianjun; Jensen, Michael; Wiesmann, Marion; Wuerthner, Jens; Graus-Porta, Diana
  • Erschienen: American Association for Cancer Research (AACR), 2014
  • Erschienen in: Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/1538-7445.am2014-2909
  • ISSN: 0008-5472; 1538-7445
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Patient selection biomarkers are essential for the successful and rapid development of emerging targeted anti-cancer therapeutics. In this study we have identified a novel patient selection strategy for NVP-CGM097, a p53-Mdm2 inhibitor currently in a Phase I clinical trial (NCT01760525). We have analyzed the sensitivity of over 500 cell lines from the “Cancer Cell Line Encyclopedia” to the p53-Mdm2 inhibitor in cell viability assays, and intersected response data with information on gene expression and genomic alterations. This analysis has led to the identification of a gene signature consisting of 13 genes, as a predictor for sensitivity to NVP-CGM097. Interestingly, these 13 genes are known p53 downstream target genes, supporting the hypothesis that the identified gene signature is reflective of the p53 pathway functionality in sensitive cell lines. We show the performance of the signature as ROC and Precision-Recall curves in cell lines as well as in a number of human primary tumor xenografts, both unselected as well as pre-selected for p53 wild-type status. Work is now ongoing to validate this gene signature using baseline tumor biopsy samples and RECIST-based efficacy readouts in the current Phase I clinical trial.</jats:p> <jats:p>Citation Format: Sebastien Jeay, Swann Gaulis, Stéphane Ferretti, Geneviève Albrecht, Louise Barys, Daniel Guthy, Ensar Halilovic, Moriko Ito, Masato Murakami, Astrid Pornon, Stephan Ruetz, Kavitha Venkatesan, Jianjun Yu, Michael Jensen, Marion Wiesmann, Jens Wuerthner, Diana Graus-Porta. A gene signature composed of 13 p53 target genes predicts for response to NVP-CGM097, a novel p53-Mdm2 inhibitor, in cell lines and in human primary tumor xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2909. doi:10.1158/1538-7445.AM2014-2909</jats:p>
  • Zugangsstatus: Freier Zugang