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@ARTICLE{Bull:301728,
      author       = {E. C. Bull and A. Singh and A. M. Harden and K. Soanes and
                      H. Habash and L. Toracchio and M. Carrabotta and C. Schreck
                      and K. M. Shah and P. V. Riestra and M. Chantoiseau and M.
                      E. M. Da Costa and G. Moquin-Beaudry and P. Pantziarka and
                      E. A. Essiet and C. Gerrand and A. Gartland and L. Bojmar
                      and A. Fahlgren and A. Marchais and E. Papakonstantinou and
                      E. M. Tomazou and D. Surdez and D. Heymann and F.
                      Cidre-Aranaz$^*$ and O. Fromigue and D. W. Sexton and N.
                      Herold and T. G. P. Grünewald$^*$ and K. Scotlandi and M.
                      Nathrath and D. Green},
      title        = {{T}argeting metastasis in paediatric bone sarcomas.},
      journal      = {Molecular cancer},
      volume       = {24},
      number       = {1},
      issn         = {1476-4598},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2025-01120},
      pages        = {153},
      year         = {2025},
      abstract     = {Paediatric bone sarcomas (e.g. Ewing sarcoma, osteosarcoma)
                      comprise significant biological and clinical heterogeneity.
                      This extreme heterogeneity affects response to systemic
                      therapy, facilitates inherent and acquired drug resistance
                      and possibly underpins the origins of metastatic disease, a
                      key component implicit in cancer related death. Across all
                      cancers, metastatic models have offered competing accounts
                      on when dissemination occurs, either early or late during
                      tumorigenesis, whether metastases at different foci arise
                      independently and directly from the primary tumour or give
                      rise to each other, i.e. metastases-to-metastases
                      dissemination, and whether cell exchange occurs between
                      synchronously growing lesions. Although it is probable that
                      all the above mechanisms can lead to metastatic disease,
                      clinical observations indicate that distinct modes of
                      metastasis might predominate in different cancers. Around
                      $70\%$ of patients with bone sarcoma experience metastasis
                      during their disease course but the fundamental molecular
                      and cell mechanisms underlying spread are equivocal. Newer
                      therapies such as tyrosine kinase inhibitors have shown
                      promise in reducing metastatic relapse in trials,
                      nonetheless, not all patients respond and 5-year overall
                      survival remains at ~ $50\%.$ Better understanding of
                      potential bone sarcoma biological subgroups, the role of the
                      tumour immune microenvironment, factors that promote
                      metastasis and clinical biomarkers of prognosis and drug
                      response are required to make progress. In this review, we
                      provide a comprehensive overview of the approaches to manage
                      paediatric patients with metastatic Ewing sarcoma and
                      osteosarcoma. We describe the molecular basis of the tumour
                      immune microenvironment, cell plasticity, circulating tumour
                      cells and the development of the pre-metastatic niche, all
                      required for successful distant colonisation. Finally, we
                      discuss ongoing and upcoming patient clinical trials,
                      biomarkers and gene regulatory networks amenable to the
                      development of anti-metastasis medicines.},
      subtyp        = {Review Article},
      keywords     = {Humans / Bone Neoplasms: pathology / Bone Neoplasms: drug
                      therapy / Child / Osteosarcoma: pathology / Osteosarcoma:
                      drug therapy / Neoplasm Metastasis / Tumor Microenvironment:
                      drug effects / Sarcoma, Ewing: pathology / Sarcoma, Ewing:
                      drug therapy / Molecular Targeted Therapy / Biomarkers,
                      Tumor / Prognosis / Bone (Other) / Ewing sarcoma (Other) /
                      Metastasis (Other) / Osteosarcoma (Other) / Sarcoma (Other)
                      / Biomarkers, Tumor (NLM Chemicals)},
      cin          = {B410 / HD01},
      ddc          = {570},
      cid          = {I:(DE-He78)B410-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40442778},
      doi          = {10.1186/s12943-025-02365-z},
      url          = {https://inrepo02.dkfz.de/record/301728},
}