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Redini F, Heymann D. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma. Front Oncol. 2015;5:279doi: 10.3389/fonc.2015.00279.
Redini, F., & Heymann, D. (2015). Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma. Frontiers in oncology, 5279. https://doi.org/10.3389/fonc.2015.00279
Redini, Françoise, and Heymann, Dominique. "Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma." Frontiers in oncology vol. 5 (2015): 279. doi: https://doi.org/10.3389/fonc.2015.00279
Redini F, Heymann D. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma. Front Oncol. 2015 Dec 23;5:279. doi: 10.3389/fonc.2015.00279. eCollection 2015. PMID: 26779435; PMCID: PMC4688361.
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Front Oncol. 2015 Dec 23;5:279. doi: 10.3389/fonc.2015.00279. eCollection 2015.

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

Frontiers in oncology

Françoise Redini, Dominique Heymann

Affiliations

  1. INSERM UMR_S 957, Nantes, France; Equipe labellisée Ligue contre le Cancer 2012, Nantes, France; Laboratoire de Physiopathologie de la Résorption osseuse et Thérapie des tumeurs osseuses primitives, Faculté de Médecine, Nantes, France.
  2. INSERM UMR_S 957, Nantes, France; Equipe labellisée Ligue contre le Cancer 2012, Nantes, France; Laboratoire de Physiopathologie de la Résorption osseuse et Thérapie des tumeurs osseuses primitives, Faculté de Médecine, Nantes, France; CHU Hôtel-Dieu, Nantes, France.

PMID: 26779435 PMCID: PMC4688361 DOI: 10.3389/fonc.2015.00279

Abstract

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

Keywords: 3D models; Ewing sarcoma; RANKL; bisphosphonate; bone remodeling; microenvironment; tumor bone niche

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