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Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study
Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually in the liver. When metastatic, the prognosis is poor, and few treatment options exist. Here, we investigated the feasibility of establishing patient-derived xenogr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604955/ https://www.ncbi.nlm.nih.gov/pubmed/37887557 http://dx.doi.org/10.3390/curroncol30100657 |
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author | Nemati, Fariba de Koning, Leanne Gentien, David Assayag, Franck Henry, Emilie Ait Rais, Khadija Pierron, Gaelle Mariani, Odette Nijnikoff, Michèle Champenois, Gabriel Nicolas, André Meseure, Didier Gardrat, Sophie Servant, Nicolas Hupé, Philippe Kamal, Maud Le Tourneau, Christophe Piperno-Neumann, Sophie Rodrigues, Manuel Roman-Roman, Sergio Decaudin, Didier Mariani, Pascale Cassoux, Nathalie |
author_facet | Nemati, Fariba de Koning, Leanne Gentien, David Assayag, Franck Henry, Emilie Ait Rais, Khadija Pierron, Gaelle Mariani, Odette Nijnikoff, Michèle Champenois, Gabriel Nicolas, André Meseure, Didier Gardrat, Sophie Servant, Nicolas Hupé, Philippe Kamal, Maud Le Tourneau, Christophe Piperno-Neumann, Sophie Rodrigues, Manuel Roman-Roman, Sergio Decaudin, Didier Mariani, Pascale Cassoux, Nathalie |
author_sort | Nemati, Fariba |
collection | PubMed |
description | Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually in the liver. When metastatic, the prognosis is poor, and few treatment options exist. Here, we investigated the feasibility of establishing patient-derived xenografts (PDXs) from a patient’s tumor in order to screen for therapies that the patient could benefit from. Samples obtained from 29 primary tumors and liver metastases of uveal melanoma were grafted into SCID mice. PDX models were successfully established for 35% of primary patient tumors and 67% of liver metastases. The tumor take rate was proportional to the risk of metastases. PDXs showed the same morphology, the same GNAQ/11, BAP1, and SF3B1 mutations, and the same chromosome 3 and 8q status as the corresponding patient samples. Six PDX models were challenged with two compounds for 4 weeks. We show that, for 31% of patients with high or intermediate risk of metastasis, the timing to obtain efficacy results on PDX models derived from their primary tumors was compatible with the selection of the therapy to treat the patient after relapse. PDXs could thus be a valid tool (“avatar”) to select the best personalized therapy for one third of patients that are most at risk of relapse. |
format | Online Article Text |
id | pubmed-10604955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106049552023-10-28 Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study Nemati, Fariba de Koning, Leanne Gentien, David Assayag, Franck Henry, Emilie Ait Rais, Khadija Pierron, Gaelle Mariani, Odette Nijnikoff, Michèle Champenois, Gabriel Nicolas, André Meseure, Didier Gardrat, Sophie Servant, Nicolas Hupé, Philippe Kamal, Maud Le Tourneau, Christophe Piperno-Neumann, Sophie Rodrigues, Manuel Roman-Roman, Sergio Decaudin, Didier Mariani, Pascale Cassoux, Nathalie Curr Oncol Article Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually in the liver. When metastatic, the prognosis is poor, and few treatment options exist. Here, we investigated the feasibility of establishing patient-derived xenografts (PDXs) from a patient’s tumor in order to screen for therapies that the patient could benefit from. Samples obtained from 29 primary tumors and liver metastases of uveal melanoma were grafted into SCID mice. PDX models were successfully established for 35% of primary patient tumors and 67% of liver metastases. The tumor take rate was proportional to the risk of metastases. PDXs showed the same morphology, the same GNAQ/11, BAP1, and SF3B1 mutations, and the same chromosome 3 and 8q status as the corresponding patient samples. Six PDX models were challenged with two compounds for 4 weeks. We show that, for 31% of patients with high or intermediate risk of metastasis, the timing to obtain efficacy results on PDX models derived from their primary tumors was compatible with the selection of the therapy to treat the patient after relapse. PDXs could thus be a valid tool (“avatar”) to select the best personalized therapy for one third of patients that are most at risk of relapse. MDPI 2023-10-11 /pmc/articles/PMC10604955/ /pubmed/37887557 http://dx.doi.org/10.3390/curroncol30100657 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nemati, Fariba de Koning, Leanne Gentien, David Assayag, Franck Henry, Emilie Ait Rais, Khadija Pierron, Gaelle Mariani, Odette Nijnikoff, Michèle Champenois, Gabriel Nicolas, André Meseure, Didier Gardrat, Sophie Servant, Nicolas Hupé, Philippe Kamal, Maud Le Tourneau, Christophe Piperno-Neumann, Sophie Rodrigues, Manuel Roman-Roman, Sergio Decaudin, Didier Mariani, Pascale Cassoux, Nathalie Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title | Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title_full | Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title_fullStr | Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title_full_unstemmed | Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title_short | Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study |
title_sort | patient derived xenografts (pdx) models as an avatar to assess personalized therapy options in uveal melanoma: a feasibility study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604955/ https://www.ncbi.nlm.nih.gov/pubmed/37887557 http://dx.doi.org/10.3390/curroncol30100657 |
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