Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma
Osteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting bone. It is characterized by a complex genotype, mainly due to the high frequency of chromothripsis, which leads to multiple somatic copy number alterations and structural rearrangements. Any effort to design genome-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/416 |
| _version_ | 1797396294178701312 |
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| author | Lorena Landuzzi Maria Cristina Manara Pier-Luigi Lollini Katia Scotlandi |
| author_facet | Lorena Landuzzi Maria Cristina Manara Pier-Luigi Lollini Katia Scotlandi |
| author_sort | Lorena Landuzzi |
| collection | DOAJ |
| description | Osteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting bone. It is characterized by a complex genotype, mainly due to the high frequency of chromothripsis, which leads to multiple somatic copy number alterations and structural rearrangements. Any effort to design genome-driven therapies must therefore consider such high inter- and intra-tumor heterogeneity. Therefore, many laboratories and international networks are developing and sharing OS patient-derived xenografts (OS PDX) to broaden the availability of models that reproduce OS complex clinical heterogeneity. OS PDXs, and new cell lines derived from PDXs, faithfully preserve tumor heterogeneity, genetic, and epigenetic features and are thus valuable tools for predicting drug responses. Here, we review recent achievements concerning OS PDXs, summarizing the methods used to obtain ectopic and orthotopic xenografts and to fully characterize these models. The availability of OS PDXs across the many international PDX platforms and their possible use in PDX clinical trials are also described. We recommend the coupling of next-generation sequencing (NGS) data analysis with functional studies in OS PDXs, as well as the setup of OS PDX clinical trials and co-clinical trials, to enhance the predictive power of experimental evidence and to accelerate the clinical translation of effective genome-guided therapies for this aggressive disease. |
| first_indexed | 2024-03-09T00:48:16Z |
| format | Article |
| id | doaj.art-138948802d8745de8f714939cfc48066 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:48:16Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-138948802d8745de8f714939cfc480662023-12-11T17:19:31ZengMDPI AGCells2073-44092021-02-0110241610.3390/cells10020416Patient Derived Xenografts for Genome-Driven Therapy of OsteosarcomaLorena Landuzzi0Maria Cristina Manara1Pier-Luigi Lollini2Katia Scotlandi3Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyInterdepartmental Center for Cancer Research (CIRC), University of Bologna, 40138 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyOsteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting bone. It is characterized by a complex genotype, mainly due to the high frequency of chromothripsis, which leads to multiple somatic copy number alterations and structural rearrangements. Any effort to design genome-driven therapies must therefore consider such high inter- and intra-tumor heterogeneity. Therefore, many laboratories and international networks are developing and sharing OS patient-derived xenografts (OS PDX) to broaden the availability of models that reproduce OS complex clinical heterogeneity. OS PDXs, and new cell lines derived from PDXs, faithfully preserve tumor heterogeneity, genetic, and epigenetic features and are thus valuable tools for predicting drug responses. Here, we review recent achievements concerning OS PDXs, summarizing the methods used to obtain ectopic and orthotopic xenografts and to fully characterize these models. The availability of OS PDXs across the many international PDX platforms and their possible use in PDX clinical trials are also described. We recommend the coupling of next-generation sequencing (NGS) data analysis with functional studies in OS PDXs, as well as the setup of OS PDX clinical trials and co-clinical trials, to enhance the predictive power of experimental evidence and to accelerate the clinical translation of effective genome-guided therapies for this aggressive disease.https://www.mdpi.com/2073-4409/10/2/416osteosarcomapatient-derived xenograft (PDX)PDX-derived cell linesmouse PDX clinical trialgenome-driven therapypersonalized therapy. |
| spellingShingle | Lorena Landuzzi Maria Cristina Manara Pier-Luigi Lollini Katia Scotlandi Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma Cells osteosarcoma patient-derived xenograft (PDX) PDX-derived cell lines mouse PDX clinical trial genome-driven therapy personalized therapy. |
| title | Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma |
| title_full | Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma |
| title_fullStr | Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma |
| title_full_unstemmed | Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma |
| title_short | Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma |
| title_sort | patient derived xenografts for genome driven therapy of osteosarcoma |
| topic | osteosarcoma patient-derived xenograft (PDX) PDX-derived cell lines mouse PDX clinical trial genome-driven therapy personalized therapy. |
| url | https://www.mdpi.com/2073-4409/10/2/416 |
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