Abstract LB-042: Xenopatients help in redefining medical therapeutic algorithms in high risk ovarian cancer

Abstract

Abstract Platinum-based chemotherapy is the recommended first-line treatment for high-grade serous (HGS) epithelial ovarian cancer (EOC). However, most patients relapse because of platinum refractory/resistant disease. We aimed at assessing whether other drugs, commonly used to treat relapsed HGS-EOC and poorly active in this clinical setting, might be more effective against chemotherapy-naïve cancers. We collected samples of advanced HGS-EOC from the same patients before and after neo-adjuvant platinum-based chemotherapy. Samples were propagated as Patient Derived Xenografts (PDXs) in immunocompromised mice (“xenopatients”). Xenopatients were treated with carboplatin, gemcitabine, pegylated liposomal doxorubicin (PLD) and trabectedin. One patient was studied who experienced clinically platinum-sensitivity first and then discordant responses of different tumor sites to platinum re-challenge. PDXs derived from this patient before chemotherapy showed responsiveness to carboplatin, trabectedin and gemcitabine. The PDXs from the same patient after chemotherapy did no longer respond to trabectedin and gemcitabine and showed a heterogeneous response to carboplatin. Expression profiling showed that loss of responsiveness to drugs of the post-chemotherapy PDXs was associated with the up-regulation of NR2F2 gene expression. A second patient with platinum refractory HGS-EOC responded poorly to PLD as second-line treatment. PDXs obtained from this patient's tumor before chemotherapy showed a complete response to PLD, which was lost in the post-chemotherapy PDXs. Response to PLD was associated with the over-expression of the TOP2A protein, which was lost in the post-chemotherapy PDXs. Thus, PDXs demonstrated that chemotherapy-naïve HGS-EOC might display susceptibility to agents not used commonly as first line treatment. These data suggest the importance of tailoring chemotherapy. Citation Format: Jessica Erriquez, Martina Olivero, Gloria Mittica, Maria Stella Scalzo, Marco Vaira, Michele De Simone, Riccardo Ponzone, Dionyssios Katsaros, Massimo Aglietta, Raffaele Calogero, Maria Flavia Di Renzo, Giorgio Valabrega. Xenopatients help in redefining medical therapeutic algorithms in high risk ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-042.