Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor
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 MPN...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Juana Fernández-Rodríguez [verfasserIn] Andrés Morales La Madrid [verfasserIn] Bernat Gel [verfasserIn] Alicia Castañeda Heredia [verfasserIn] Héctor Salvador [verfasserIn] María Martínez-Iniesta [verfasserIn] Catia Moutinho [verfasserIn] Jordi Morata [verfasserIn] Holger Heyn [verfasserIn] Ignacio Blanco [verfasserIn] Edgar Creus-Bachiller [verfasserIn] Gabriel Capella [verfasserIn] Lourdes Farré [verfasserIn] August Vidal [verfasserIn] Francisco Soldado [verfasserIn] Lucas Krauel [verfasserIn] Mariona Suñol [verfasserIn] Eduard Serra [verfasserIn] Alberto Villanueva [verfasserIn] Conxi Lázaro [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Übergeordnetes Werk: |
In: Therapeutic Advances in Medical Oncology - SAGE Publishing, 2018, 12(2020) |
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| Übergeordnetes Werk: |
volume:12 ; year:2020 |
| Links: |
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| DOI / URN: |
10.1177/1758835920929579 |
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| Katalog-ID: |
DOAJ046232745 |
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| 520 | |a 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 (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. | ||
| 653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
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| 700 | 0 | |a Alicia Castañeda Heredia |e verfasserin |4 aut | |
| 700 | 0 | |a Héctor Salvador |e verfasserin |4 aut | |
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10.1177/1758835920929579 doi (DE-627)DOAJ046232745 (DE-599)DOAJ02b45471cb414606bd6321400e909f5f DE-627 ger DE-627 rakwb eng RC254-282 Juana Fernández-Rodríguez verfasserin aut Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Andrés Morales La Madrid verfasserin aut Bernat Gel verfasserin aut Alicia Castañeda Heredia verfasserin aut Héctor Salvador verfasserin aut María Martínez-Iniesta verfasserin aut Catia Moutinho verfasserin aut Jordi Morata verfasserin aut Holger Heyn verfasserin aut Ignacio Blanco verfasserin aut Edgar Creus-Bachiller verfasserin aut Gabriel Capella verfasserin aut Lourdes Farré verfasserin aut August Vidal verfasserin aut Francisco Soldado verfasserin aut Lucas Krauel verfasserin aut Mariona Suñol verfasserin aut Eduard Serra verfasserin aut Alberto Villanueva verfasserin aut Conxi Lázaro verfasserin aut In Therapeutic Advances in Medical Oncology SAGE Publishing, 2018 12(2020) (DE-627)604082282 (DE-600)2503443-1 17588359 nnns volume:12 year:2020 https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/article/02b45471cb414606bd6321400e909f5f kostenfrei https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/toc/1758-8359 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_121 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2889 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 |
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10.1177/1758835920929579 doi (DE-627)DOAJ046232745 (DE-599)DOAJ02b45471cb414606bd6321400e909f5f DE-627 ger DE-627 rakwb eng RC254-282 Juana Fernández-Rodríguez verfasserin aut Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Andrés Morales La Madrid verfasserin aut Bernat Gel verfasserin aut Alicia Castañeda Heredia verfasserin aut Héctor Salvador verfasserin aut María Martínez-Iniesta verfasserin aut Catia Moutinho verfasserin aut Jordi Morata verfasserin aut Holger Heyn verfasserin aut Ignacio Blanco verfasserin aut Edgar Creus-Bachiller verfasserin aut Gabriel Capella verfasserin aut Lourdes Farré verfasserin aut August Vidal verfasserin aut Francisco Soldado verfasserin aut Lucas Krauel verfasserin aut Mariona Suñol verfasserin aut Eduard Serra verfasserin aut Alberto Villanueva verfasserin aut Conxi Lázaro verfasserin aut In Therapeutic Advances in Medical Oncology SAGE Publishing, 2018 12(2020) (DE-627)604082282 (DE-600)2503443-1 17588359 nnns volume:12 year:2020 https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/article/02b45471cb414606bd6321400e909f5f kostenfrei https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/toc/1758-8359 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_121 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2889 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 |
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10.1177/1758835920929579 doi (DE-627)DOAJ046232745 (DE-599)DOAJ02b45471cb414606bd6321400e909f5f DE-627 ger DE-627 rakwb eng RC254-282 Juana Fernández-Rodríguez verfasserin aut Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Andrés Morales La Madrid verfasserin aut Bernat Gel verfasserin aut Alicia Castañeda Heredia verfasserin aut Héctor Salvador verfasserin aut María Martínez-Iniesta verfasserin aut Catia Moutinho verfasserin aut Jordi Morata verfasserin aut Holger Heyn verfasserin aut Ignacio Blanco verfasserin aut Edgar Creus-Bachiller verfasserin aut Gabriel Capella verfasserin aut Lourdes Farré verfasserin aut August Vidal verfasserin aut Francisco Soldado verfasserin aut Lucas Krauel verfasserin aut Mariona Suñol verfasserin aut Eduard Serra verfasserin aut Alberto Villanueva verfasserin aut Conxi Lázaro verfasserin aut In Therapeutic Advances in Medical Oncology SAGE Publishing, 2018 12(2020) (DE-627)604082282 (DE-600)2503443-1 17588359 nnns volume:12 year:2020 https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/article/02b45471cb414606bd6321400e909f5f kostenfrei https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/toc/1758-8359 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_121 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2889 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 |
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10.1177/1758835920929579 doi (DE-627)DOAJ046232745 (DE-599)DOAJ02b45471cb414606bd6321400e909f5f DE-627 ger DE-627 rakwb eng RC254-282 Juana Fernández-Rodríguez verfasserin aut Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Andrés Morales La Madrid verfasserin aut Bernat Gel verfasserin aut Alicia Castañeda Heredia verfasserin aut Héctor Salvador verfasserin aut María Martínez-Iniesta verfasserin aut Catia Moutinho verfasserin aut Jordi Morata verfasserin aut Holger Heyn verfasserin aut Ignacio Blanco verfasserin aut Edgar Creus-Bachiller verfasserin aut Gabriel Capella verfasserin aut Lourdes Farré verfasserin aut August Vidal verfasserin aut Francisco Soldado verfasserin aut Lucas Krauel verfasserin aut Mariona Suñol verfasserin aut Eduard Serra verfasserin aut Alberto Villanueva verfasserin aut Conxi Lázaro verfasserin aut In Therapeutic Advances in Medical Oncology SAGE Publishing, 2018 12(2020) (DE-627)604082282 (DE-600)2503443-1 17588359 nnns volume:12 year:2020 https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/article/02b45471cb414606bd6321400e909f5f kostenfrei https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/toc/1758-8359 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_121 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2889 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 |
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10.1177/1758835920929579 doi (DE-627)DOAJ046232745 (DE-599)DOAJ02b45471cb414606bd6321400e909f5f DE-627 ger DE-627 rakwb eng RC254-282 Juana Fernández-Rodríguez verfasserin aut Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Andrés Morales La Madrid verfasserin aut Bernat Gel verfasserin aut Alicia Castañeda Heredia verfasserin aut Héctor Salvador verfasserin aut María Martínez-Iniesta verfasserin aut Catia Moutinho verfasserin aut Jordi Morata verfasserin aut Holger Heyn verfasserin aut Ignacio Blanco verfasserin aut Edgar Creus-Bachiller verfasserin aut Gabriel Capella verfasserin aut Lourdes Farré verfasserin aut August Vidal verfasserin aut Francisco Soldado verfasserin aut Lucas Krauel verfasserin aut Mariona Suñol verfasserin aut Eduard Serra verfasserin aut Alberto Villanueva verfasserin aut Conxi Lázaro verfasserin aut In Therapeutic Advances in Medical Oncology SAGE Publishing, 2018 12(2020) (DE-627)604082282 (DE-600)2503443-1 17588359 nnns volume:12 year:2020 https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/article/02b45471cb414606bd6321400e909f5f kostenfrei https://doi.org/10.1177/1758835920929579 kostenfrei https://doaj.org/toc/1758-8359 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_121 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2889 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 |
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Juana Fernández-Rodríguez @@aut@@ Andrés Morales La Madrid @@aut@@ Bernat Gel @@aut@@ Alicia Castañeda Heredia @@aut@@ Héctor Salvador @@aut@@ María Martínez-Iniesta @@aut@@ Catia Moutinho @@aut@@ Jordi Morata @@aut@@ Holger Heyn @@aut@@ Ignacio Blanco @@aut@@ Edgar Creus-Bachiller @@aut@@ Gabriel Capella @@aut@@ Lourdes Farré @@aut@@ August Vidal @@aut@@ Francisco Soldado @@aut@@ Lucas Krauel @@aut@@ Mariona Suñol @@aut@@ Eduard Serra @@aut@@ Alberto Villanueva @@aut@@ Conxi Lázaro @@aut@@ |
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RC254-282 Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor |
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Juana Fernández-Rodríguez Andrés Morales La Madrid Bernat Gel Alicia Castañeda Heredia Héctor Salvador María Martínez-Iniesta Catia Moutinho Jordi Morata Holger Heyn Ignacio Blanco Edgar Creus-Bachiller Gabriel Capella Lourdes Farré August Vidal Francisco Soldado Lucas Krauel Mariona Suñol Eduard Serra Alberto Villanueva Conxi Lázaro |
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use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor |
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Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor |
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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 (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. |
| abstractGer |
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 (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. |
| abstract_unstemmed |
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 (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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