Survival rate for high grade ovarian cancer (HGOC) remains low and has not significantly evolved for several years. This poor outcome is due to several mechanisms of resistance (initial or acquired) in different context (Homologous recombination deficience, CCNE1 amplification). We developed a collection of High-grade ovarian cancer Patient Derived Xenografts (PDX) with extensive characterization (CGH, transcriptome and exome sequencing, Colombo et al, Oncotarget. 2015 Sep 29;6(29):28327-40). Our objective is to create a panel of HGOC PDX which encompasses main types of platinium sensitivity/resistance in HGOC. We selected 10 PDX models (9 serous histiotypes and one carcinosarcomas) among our collection of 39 HGOC PDXs from two patient extreme platinium response categories (resistant with a progression-free inferior to 6 months and sensible with a progression-free higher than 18 months, some of the sensitives with BRCA1 mutations). These PDXs included PDXs were grafted sub-cutaneously on nude mice and submitted to carboplatin treatment (50mg/kg twice a week, for 4 weeks) and impact on tumor growth was evaluated as well as histological characterization. For the carcinosarcomas, no selection of the epithelial or sarcomatous component upon treatment was observed. Outgrowth of the tumors after end of treatment is currently under assessment.
Remarkably, tumor PDXs response was in accordance with clinical status with complete and partial response for the sensitive PDXs; slowed growth under treatment or stabilization for resistant PDXs. Outgrowth of the tumor after the end of treatment is currently under assessment.
For each PDXs model, the large majority of the 7-9 treated tumor reacted in identical fashion if classified according to RECIST criteria with occasionally divergent responses reflecting tumor heterogeneity. Genetic and histological characterization of these outliers is ongoing.
This collection is a valuable resource to model carboplatine resistance in a well-defined context and will be the cornerstone of our future studies to conduct preclinical drugs tests, in particular for combination selected in vitro and to evaluate clonal evolution under treatment.
Citation Format: Stan P. du Manoir, Helene Delpech, Beatrice Orsetti, Jeremy Tessier, Pierre-Emmanuel Colombo, Charles G. Theillet. Correspondence between clinical patient outcome and in vivo carboplatine response of high grade ovarian cancer PDX. [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 5190.