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Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. More than a third of patients do not respond to standard therapy and urgently require alternative treatment options. Due to a high degree of inter‐ and intra‐tumoural genomic heterogeneity and complexity, recu...

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Autores principales: Ameline, Baptiste, Kovac, Michal, Nathrath, Michaela, Barenboim, Maxim, Witt, Olaf, Krieg, Andreas H, Baumhoer, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869926/
https://www.ncbi.nlm.nih.gov/pubmed/33295144
http://dx.doi.org/10.1002/cjp2.191
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author Ameline, Baptiste
Kovac, Michal
Nathrath, Michaela
Barenboim, Maxim
Witt, Olaf
Krieg, Andreas H
Baumhoer, Daniel
author_facet Ameline, Baptiste
Kovac, Michal
Nathrath, Michaela
Barenboim, Maxim
Witt, Olaf
Krieg, Andreas H
Baumhoer, Daniel
author_sort Ameline, Baptiste
collection PubMed
description Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. More than a third of patients do not respond to standard therapy and urgently require alternative treatment options. Due to a high degree of inter‐ and intra‐tumoural genomic heterogeneity and complexity, recurrent molecular alterations that could serve as prognostic predictors or therapeutic targets are still lacking in osteosarcoma. Copy number (CN) gains involving the IGF1R gene, however, have been suggested as a potential surrogate marker for treating a subset of patients with IGF1R inhibitors. In this study, we screened a large set of osteosarcomas and found specific CN gains of the IGF1R gene in 18 of 253 (7.1%) cases with corresponding IGF1R overexpression. Despite the discouraging results observed in clinical trials in other tumours so far, focusing only on selected patients with osteosarcoma that show evidence of IGF pathway activation might represent a promising new and innovative treatment approach.
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spelling pubmed-78699262021-02-17 Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target? Ameline, Baptiste Kovac, Michal Nathrath, Michaela Barenboim, Maxim Witt, Olaf Krieg, Andreas H Baumhoer, Daniel J Pathol Clin Res Original Articles Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. More than a third of patients do not respond to standard therapy and urgently require alternative treatment options. Due to a high degree of inter‐ and intra‐tumoural genomic heterogeneity and complexity, recurrent molecular alterations that could serve as prognostic predictors or therapeutic targets are still lacking in osteosarcoma. Copy number (CN) gains involving the IGF1R gene, however, have been suggested as a potential surrogate marker for treating a subset of patients with IGF1R inhibitors. In this study, we screened a large set of osteosarcomas and found specific CN gains of the IGF1R gene in 18 of 253 (7.1%) cases with corresponding IGF1R overexpression. Despite the discouraging results observed in clinical trials in other tumours so far, focusing only on selected patients with osteosarcoma that show evidence of IGF pathway activation might represent a promising new and innovative treatment approach. John Wiley & Sons, Inc. 2020-12-08 /pmc/articles/PMC7869926/ /pubmed/33295144 http://dx.doi.org/10.1002/cjp2.191 Text en © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ameline, Baptiste
Kovac, Michal
Nathrath, Michaela
Barenboim, Maxim
Witt, Olaf
Krieg, Andreas H
Baumhoer, Daniel
Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title_full Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title_fullStr Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title_full_unstemmed Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title_short Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?
title_sort overactivation of the igf signalling pathway in osteosarcoma: a potential therapeutic target?
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869926/
https://www.ncbi.nlm.nih.gov/pubmed/33295144
http://dx.doi.org/10.1002/cjp2.191
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