Research Papers:

Xenopatients show the need for precision medicine approach to chemotherapy in ovarian cancer

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 and Giorgio Valabrega

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:26181-26191. https://doi.org/10.18632/oncotarget.8325

Metrics: PDF 1768 views  |   HTML 2357 views  |   ?  


Jessica Erriquez2,*, Martina Olivero1,2,*, Gloria Mittica1,2, Maria Stella Scalzo3, Marco Vaira2, Michele De Simone2, Riccardo Ponzone2, Dionyssios Katsaros4, Massimo Aglietta1,2, Raffaele Calogero5, Maria Flavia Di Renzo1,2, Giorgio Valabrega1,2

1Department of Oncology, University of Torino, Candiolo, Torino, Italy

2Candiolo Cancer Institute, FPO-IRCCS Candiolo, Torino, Italy

3Department of Medical Sciences, University of Torino, Torino, Italy

4Department of Surgical Sciences, Gynecologic Oncology, AO-Universitaria Città della Salute, Torino, Italy

5Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy

*These authors have contributed equally to this work

Correspondence to:

Maria Flavia Di Renzo, e-mail: [email protected]

Keywords: ovarian cancer, chemotherapy, patient derived xenograft

Received: December 14, 2015    Accepted: March 14, 2016    Published: March 24, 2016


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 couples of HGS-EOC samples 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 in parallel with carboplatin, gemcitabine, pegylated liposomal doxorubicin (PLD) and trabectedin. PDXs derived from a naïve HSG-EOC showed responsiveness to carboplatin, trabectedin and gemcitabine. The PDXs propagated from a tumor mass of the same patient, grown after carboplatin therapy, did no longer respond to trabectedin and gemcitabine and showed heterogeneous response to carboplatin. In line, the patient experienced clinically platinum-sensitivity first and then discordant responses of different tumor sites to platinum re-challenge. Loss of PDX responsiveness to drugs was associated with 4-fold increase of NR2F2 gene expression. PDXs from another naïve tumor showed complete response to PLD, which was lost in the PDXs derived from a mass grown in the same patient after platinum-based chemotherapy. This patient showed platinum refractoriness and responded poorly to PLD as second-line treatment. PDX response to PLD was associated with high expression of TOP2A protein. PDXs demonstrated that chemotherapy-naïve HGS-EOC might display susceptibility to agents not used commonly as first line treatment. Data suggest the importance of personalizing also chemotherapy.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8325