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Title: Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor
Author: Fernández-Rodríguez, Juana
Morales La Madrid, Andrés
Gel, Bernat
Castañeda Heredia, Alicia
Salvador, Héctor
Martínez Iniesta, María
Moutinho, Cátia
Morata, Jordi
Heyn, Holger
Blanco Guillermo, Ignacio
Creus Bachiller, Edgar
Capellá, G. (Gabriel)
Farré, Lourdes
Vidal-Bel, August
Soldado, Francisco
Krauel, Lucas
Suñol, Mariona
Serra, Eduard
Villanueva Garatachea, Alberto
Lázaro García, Conxi
Keywords: Oncologia pediàtrica
Tumors in children
Issue Date: 3-Jul-2020
Publisher: SAGE Publications
Abstract: Background: The aim of this study was to test the feasibility and utility of developing patient derived orthotopic xenograft (PDOX) models for patients with malignant peripheral nerve sheath tumors (MPNSTs) to aid therapeutic interventions in real-time. Patient-Methods: A sporadic relapsed MPNST developed in a 14-year-old boy was engrafted in mice generating a PDOX model for use in co-clinical trials after informed consent. SNP-array and exome sequencing was performed on the relapsed tumor. Genomics, drug availability and published literature guided PDOX treatments. Results: A MPNST PDOX model was generated and expanded. Analysis of the patient's relapsed tumor revealed mutations in the MAPK1, EED and CDK2NA/B genes. First, the PDOX model was treated with the same therapeutic regimen as received by the patient (everolimus and trametinib), after observing partial response, tumors were left to regrow. Regrown tumors were treated based on mutations (palbociclib and JQ1), drug availability and published literature (nabpaclitaxel; bevacizumab; sorafenib plus doxorubicin and gemcitabine plus docetaxel). The patient had a lung metastatic relapse and was treated according to PDOX results, first with nab-paclitaxel, second with sorafenib plus doxorubicin after progression, although a complete response was not achieved and multiple metastasectomies were performed. The patient is currently disease free 46 months after first relapse. Conclusion: Our results indicate the feasibility of generating MPNST-PDOX and genomic characterization to guide treatment in real-time. Although the treatment responses observed in our model did not fully recapitulate the patient's response, this pilot study identify key aspects to improve our co-clinical testing approach in real-time.
Note: Reproducció del document publicat a:
It is part of: Therapeutic Advances In Medical Oncology, 2020, vol. 12
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ISSN: 1758-8340
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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