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      Advances in Osteosarcoma

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          Abstract

          Purpose of Review

          This article gives a brief overview of the most recent developments in osteosarcoma treatment, including targeting of signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and the identification of new therapeutic targets to face this highly heterogeneous disease.

          Recent Findings

          Osteosarcoma is one of the most common primary malignant bone tumors in children and young adults, with a high risk of bone and lung metastases and a 5-year survival rate around 70% in the absence of metastases and 30% if metastases are detected at the time of diagnosis. Despite the novel advances in neoadjuvant chemotherapy, the effective treatment for osteosarcoma has not improved in the last 4 decades. The emergence of immunotherapy has transformed the paradigm of treatment, focusing therapeutic strategies on the potential of immune checkpoint inhibitors. However, the most recent clinical trials show a slight improvement over the conventional polychemotherapy scheme.

          Summary

          The tumor microenvironment plays a crucial role in the pathogenesis of osteosarcoma by controlling the tumor growth, the metastatic process and the drug resistance and paved the way of new therapeutic options that must be validated by accurate pre-clinical studies and clinical trials.

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          Most cited references118

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          The human tumor microbiome is composed of tumor type–specific intracellular bacteria

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            Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

            Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma.
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              Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer

              Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs, and to maintain redox homeostasis. One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT). SLC7A11 promotes cystine uptake and glutathione biosynthesis, resulting in protection from oxidative stress and ferroptotic cell death. Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells. This review discusses the roles of SLC7A11 in regulating the antioxidant response and nutrient dependency of cancer cells, explores our current understanding of SLC7A11 regulation in cancer metabolism, and highlights key open questions for future studies in this emerging research area. A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
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                Author and article information

                Contributors
                Javier.munoz@ico.unicancer.fr
                dominique.heymann@univ-nantes.fr
                Journal
                Curr Osteoporos Rep
                Curr Osteoporos Rep
                Current Osteoporosis Reports
                Springer US (New York )
                1544-1873
                1544-2241
                17 June 2023
                17 June 2023
                2023
                : 21
                : 4
                : 330-343
                Affiliations
                [1 ]GRID grid.4817.a, ISNI 0000 0001 2189 0784, Nantes Université, CNRS, UMR6286, US2B, , Biological Sciences and Biotechnologies unit, ; 44322 Nantes, France
                [2 ]GRID grid.418191.4, ISNI 0000 0000 9437 3027, Institut de Cancérologie de l’Ouest, , Tumor Heterogeneity and Precision Medicine Laboratory, ; 44805 Saint-Herblain, France
                [3 ]GRID grid.412881.6, ISNI 0000 0000 8882 5269, University of Antioquia, , Department of Basic Studies, Faculty of Odontology, ; Medellin, Colombia
                [4 ]GRID grid.413776.0, ISNI 0000 0004 1937 1098, Sorbonne Université, INSERM UMR933, , Hôpital Trousseau (AP-HP), ; 75012 Paris, France
                [5 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, University of Sheffield, , Medical School, Department of Oncology and Metabolism, ; S10 2RX, Sheffield, UK
                Author information
                https://orcid.org/0000-0002-0060-7502
                https://orcid.org/0000-0002-2978-1192
                https://orcid.org/0000-0002-3924-7372
                https://orcid.org/0000-0002-5585-8261
                https://orcid.org/0000-0001-6274-6981
                http://orcid.org/0000-0001-7777-0669
                Article
                803
                10.1007/s11914-023-00803-9
                10393907
                37329384
                cc27d813-20d5-4cf0-b8b9-cebae5a6123e
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 June 2023
                Funding
                Funded by: ICO Cancer center
                Award ID: Internal support
                Award Recipient :
                Funded by: Région des Pays de la loire
                Award ID: Thèse Tandem Program
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2023

                Orthopedics
                osteosarcoma,immunotherapy,tumor targeted therapy,immune checkpoint inhibitor,tumor microenvironment,personalized medicine

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