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© 2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability
Author
Pierrevelcin, Marina; Fuchs, Quentin; Lhermitte, Benoit; Messé, Melissa; Guérin, Eric  VIAFID ORCID Logo  ; Weingertner, Noelle; Martin, Sophie; Lelong-Rebel, Isabelle; Nazon, Charlotte; Dontenwill, Monique; Entz-Werlé, Natacha
First page
1998
Publication year
2020
Publication date
2020
Publisher
MDPI AG
e-ISSN
20734409
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2440307976
Copyright
© 2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.