Bone cancer articles within Nature Communications

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  • Article
    | Open Access

    Proteomic, transcriptomic, and genomic analysis has shown osteosarcoma (OS) to be a complex and heterogenous disease but revealed little about its carcinogenesis or potential therapeutic targets. Here, the authors profile the RNA interactome, transcriptome and proteome of cells derived from OS patients, identifying a targetable vulnerability to translation inhibition.

    • Yang Zhou
    • , Partho Sarothi Ray
    •  & Andreas E. Kulozik

  • Article
    | Open Access

    Here, the authors develop a hybrid agent-based model to quantify the contributions of intrinsic cellular mechanisms and bone ecosystem factors to therapy resistance in multiple myeloma. They show that intrinsic mechanisms are essential for resistance, and that the bone microenvironment provides a protective niche that increases the likelihood.

    • Ryan T. Bishop
    • , Anna K. Miller
    •  & David Basanta

  • Article
    | Open Access

    ALT cells use an alternative lengthening mechanism of telomeres and bear telomeric DNA damage with increased levels of damage-induced long non-coding RNA. Here the AUs show that antisense oligonucleotides (ASO) targeting such RNAs can induce ALT cancer cells selective cell death.

    • Ilaria Rosso
    • , Corey Jones-Weinert
    •  & Fabrizio d’Adda di Fagagna

  • Article
    | Open Access

    Cancer cells possess unique molecular features that can confer an increased dependence on specific genes. Here, the authors use CRISPR-Cas9 screens to identify selectively essential genes and therapeutic targets in chordoma.

    • Tanaz Sharifnia
    • , Mathias J. Wawer
    •  & Stuart L. Schreiber

  • Article
    | Open Access

    The TAM family of receptor tyrosine kinases exerts pleiotropic functions in health and disease. Here, the authors show that TAM receptors control osteoblastic bone formation and identified MERTK as a novel target for bone anabolic therapy and mitigation of bone metastasis including its associated osteolytic bone disease

    • Janik Engelmann
    • , Jennifer Zarrer
    •  & Sonja Loges

  • Article
    | Open Access

    Chemo-resistance and immune evasion are major challenges in osteosarcoma treatment. Here the authors show that doxorubicin promotes IL-18 secretion by tumor associated macrophages inducing LAT2-dependent CD47 upregulation in osteosarcoma cells, suggesting LAT2 inhibition as a therapeutic option in combination with doxorubicin.

    • Zenan Wang
    • , Binghao Li
    •  & Zhaoming Ye

  • Article
    | Open Access

    There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.

    • Kaiyuan Wang
    • , Christopher R. Donnelly
    •  & Ru-Rong Ji

  • Article
    | Open Access

    Bone metastases are associated with poor prognosis in patients with breast cancer and limited therapeutic options. Here the authors exploit near-infrared light responsive macrophages for the tumor-selective delivery of oxaliplatin prodrug for chemo-photodynamic therapy of primary and bone metastatic breast cancer.

    • Yanjuan Huang
    • , Zilin Guan
    •  & Chunshun Zhao

  • Article
    | Open Access

    The effects of bone-marrow derived MSCs on prostate cancer cells remain unknown. Here the authors show that MSC-derived IL-28 induces prostate cancer cell apoptosis via IL-28Rα-STAT1 signalling, while acquired resistance to apoptosis is associated with a shift in IL-28Rα signalling via STAT1 to STAT3.

    • Jeremy J. McGuire
    • , Jeremy S. Frieling
    •  & Conor C. Lynch

  • Article
    | Open Access

    The histone variant mutation H3.3-G34W occurs in the majority of giant cell tumor of bone (GCTB). By profiling patient-derived GCTB tumor cells, the authors show that this mutation associates with epigenetic alterations in heterochromatic and bivalent regions that contribute to an impaired osteogenic differentiation and the osteolytic phenotype of GCTB.

    • Pavlo Lutsik
    • , Annika Baude
    •  & Christoph Plass

  • Article
    | Open Access

    The efficacy of immune checkpoint inhibitors (ICI) in osteosarcoma has been limited. Here, the authors investigate the immunogenomic landscape of osteosarcoma, and integrated analyses highlight features related to a suppressed immune microenvironment.

    • Chia-Chin Wu
    • , Hannah C. Beird
    •  & P. Andrew Futreal

  • Article
    | Open Access

    Interactions between germline variants and somatic mutations is a relatively unexplored topic in cancer. Here, in Ewing sarcoma, the authors show that binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls MYBL2, whose high expression correlates with prognosis.

    • Julian Musa
    • , Florencia Cidre-Aranaz
    •  & Thomas G. P. Grünewald

  • Article
    | Open Access

    Osteosarcoma is a heterogeneous bone tumour with a high mutational rate. Here the authors use an RGB-based single-cell tracking system to track clonal dynamics in a mouse model of osteosarcoma, which their findings indicate follows a neutral evolution model in which different clones simultaneously coexist and propagate.

    • Stefano Gambera
    • , Ander Abarrategi
    •  & Javier García-Castro

  • Article
    | Open Access

    FOS has been linked to bone tumour pathogenesis, and viral homologue v-fos causes osteosarcoma in mice. Here, the authors report rearrangement of FOS and its paralogue FOSB in osteoblastoma and osteoid osteoma, revealing human bone tumours that are defined by mutations of FOS and FOSB.

    • Matthew W. Fittall
    • , William Mifsud
    •  & Sam Behjati

  • Article
    | Open Access

    Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

    • Patrick S. Tarpey
    • , Sam Behjati
    •  & Peter J. Campbell

  • Article
    | Open Access

    The ability of cancer cells to survive in anchorage-independent conditions correlates with cancer aggressiveness. Here, by screening a human whole-genome shRNA library for the ability of osteosarcoma cells to form spheres in vitro, the authors identify a role for TMIGD3 isoform 1 in suppressing the metastatic potential of osteosarcoma.

    • Swathi V. Iyer
    • , Atul Ranjan
    •  & Tomoo Iwakuma

  • Article
    | Open Access

    Osteosarcomas are a heterogenous group of tumours and little is known about how these tumours evolve. Here, Kovac et al. use exome sequencing and discover that although no driver gene explains the majority of these tumours, they are characterized by specific mutation signatures and genomic instability typical of BRCA1/2-deficient tumours.

    • Michal Kovac
    • , Claudia Blattmann
    •  & Daniel Baumhoer

  • Article |

    Transcriptional regulators Sox2 and YAP maintain expression of stemness genes in normal and cancerous cells. Here the authors show that, in osteosarcomas, Sox2 activates YAP by directly repressing transcription of its upstream negative regulators Nf2 and WWC1, promoting cancer cell stemness.

    • Upal Basu-Roy
    • , N. Sumru Bayin
    •  & Claudio Basilico

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