Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability
Osteosarcoma is the most frequent primary bone tumor diagnosed during adolescence and young adulthood. It is associated with the worst outcomes in the case of poor response to chemotherapy and in metastatic disease. While no molecular biomarkers are clearly and currently associated with those worse...
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MDPI AG
2020-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1998 |
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| author | Marina Pierrevelcin Quentin Fuchs Benoit Lhermitte Melissa Messé Eric Guérin Noelle Weingertner Sophie Martin Isabelle Lelong-Rebel Charlotte Nazon Monique Dontenwill Natacha Entz-Werlé |
| author_facet | Marina Pierrevelcin Quentin Fuchs Benoit Lhermitte Melissa Messé Eric Guérin Noelle Weingertner Sophie Martin Isabelle Lelong-Rebel Charlotte Nazon Monique Dontenwill Natacha Entz-Werlé |
| author_sort | Marina Pierrevelcin |
| collection | DOAJ |
| description | Osteosarcoma is the most frequent primary bone tumor diagnosed during adolescence and young adulthood. It is associated with the worst outcomes in the case of poor response to chemotherapy and in metastatic disease. While no molecular biomarkers are clearly and currently associated with those worse situations, the study of pathways involved in the high level of tumor necrosis and in the immune/metabolic intra-tumor environment seems to be a way to understand these resistant and progressive osteosarcomas. In this review, we provide an updated overview of the role of hypoxia in osteosarcoma oncogenesis, progression and during treatment. We describe the role of normoxic/hypoxic environment in normal tissues, bones and osteosarcomas to understand their role and to estimate their druggability. We focus particularly on the role of intra-tumor hypoxia in osteosarcoma cell resistance to treatments and its impact in its endogenous immune component. Together, these previously published observations conduct us to present potential perspectives on the use of therapies targeting hypoxia pathways. These therapies could afford new treatment approaches in this bone cancer. Nevertheless, to study the osteosarcoma cell druggability, we now need specific in vitro models closely mimicking the tumor, its intra-tumor hypoxia and the immune microenvironment to more accurately predict treatment efficacy and be complementary to mouse models. |
| first_indexed | 2024-03-10T16:41:44Z |
| format | Article |
| id | doaj.art-3f18cf44bcb14cb1ae091e1498d65168 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:41:44Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3f18cf44bcb14cb1ae091e1498d651682023-11-20T11:56:55ZengMDPI AGCells2073-44092020-08-0199199810.3390/cells9091998Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their DruggabilityMarina Pierrevelcin0Quentin Fuchs1Benoit Lhermitte2Melissa Messé3Eric Guérin4Noelle Weingertner5Sophie Martin6Isabelle Lelong-Rebel7Charlotte Nazon8Monique Dontenwill9Natacha Entz-Werlé10Laboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceOncobiology, Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, 67098 Strasbourg, FrancePathology Department, University Hospital of Strasbourg, 67098 Strasbourg, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FrancePediatric Oncohematology Unit, University Hospital of Strasbourg, 67098 Strasbourg, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceLaboratory of Bioimaging and Pathologies, UMR CNRS 7021, 67405 Illkirch, FranceOsteosarcoma is the most frequent primary bone tumor diagnosed during adolescence and young adulthood. It is associated with the worst outcomes in the case of poor response to chemotherapy and in metastatic disease. While no molecular biomarkers are clearly and currently associated with those worse situations, the study of pathways involved in the high level of tumor necrosis and in the immune/metabolic intra-tumor environment seems to be a way to understand these resistant and progressive osteosarcomas. In this review, we provide an updated overview of the role of hypoxia in osteosarcoma oncogenesis, progression and during treatment. We describe the role of normoxic/hypoxic environment in normal tissues, bones and osteosarcomas to understand their role and to estimate their druggability. We focus particularly on the role of intra-tumor hypoxia in osteosarcoma cell resistance to treatments and its impact in its endogenous immune component. Together, these previously published observations conduct us to present potential perspectives on the use of therapies targeting hypoxia pathways. These therapies could afford new treatment approaches in this bone cancer. Nevertheless, to study the osteosarcoma cell druggability, we now need specific in vitro models closely mimicking the tumor, its intra-tumor hypoxia and the immune microenvironment to more accurately predict treatment efficacy and be complementary to mouse models.https://www.mdpi.com/2073-4409/9/9/1998osteosarcomahypoxiaprogressionimmunitydruggabilitypreclinical models |
| spellingShingle | Marina Pierrevelcin Quentin Fuchs Benoit Lhermitte Melissa Messé Eric Guérin Noelle Weingertner Sophie Martin Isabelle Lelong-Rebel Charlotte Nazon Monique Dontenwill Natacha Entz-Werlé Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability Cells osteosarcoma hypoxia progression immunity druggability preclinical models |
| title | Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability |
| title_full | Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability |
| title_fullStr | Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability |
| title_full_unstemmed | Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability |
| title_short | Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability |
| title_sort | focus on hypoxia related pathways in pediatric osteosarcomas and their druggability |
| topic | osteosarcoma hypoxia progression immunity druggability preclinical models |
| url | https://www.mdpi.com/2073-4409/9/9/1998 |
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