AI Article Synopsis

  • - This study aimed to evaluate the development of patient-derived orthotopic xenograft (PDOX) models for malignant peripheral nerve sheath tumors (MPNSTs) to enhance real-time therapeutic interventions.
  • - A 14-year-old boy's relapsed MPNST was used to create a PDOX model, involving genomic analysis to guide treatment strategies, including several chemotherapy regimens.
  • - Although the PDOX model showed partial treatment responses that did not fully match the patient's outcomes, it demonstrated the potential for real-time treatment guidance and identified areas for improving co-clinical testing approaches.

Article 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 , and 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 (nab-paclitaxel; 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339074PMC
http://dx.doi.org/10.1177/1758835920929579DOI Listing

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