% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Calandrini:170414,
      author       = {C. Calandrini and S. R. van Hooff and I. Paassen and D.
                      Ayyildiz and S. Derakhshan and M. E. M. Dolman and K. P. S.
                      Langenberg and M. van de Ven and C. de Heus and N. Liv and
                      M. Kool$^*$ and R. R. de Krijger and G. A. M. Tytgat and M.
                      M. van den Heuvel-Eibrink and J. J. Molenaar and J. Drost},
      title        = {{O}rganoid-based drug screening reveals neddylation as
                      therapeutic target for malignant rhabdoid tumors.},
      journal      = {Cell reports},
      volume       = {36},
      number       = {8},
      issn         = {2211-1247},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2021-01917},
      pages        = {109568},
      year         = {2021},
      abstract     = {Malignant rhabdoid tumors (MRTs) represent one of the most
                      aggressive childhood malignancies. No effective treatment
                      options are available, and prognosis is, therefore, dismal.
                      Previous studies have demonstrated that tumor organoids
                      capture the heterogeneity of patient tumors and can be used
                      to predict patient response to therapy. Here, we perform
                      drug screening on patient-derived normal and tumor organoids
                      to identify MRT-specific therapeutic vulnerabilities. We
                      identify neddylation inhibitor MLN4924 as a potential
                      therapeutic agent. Mechanistically, we find increased
                      neddylation in MRT organoids and tissues and show that
                      MLN4924 induces a cytotoxic response via upregulation of the
                      unfolded protein response. Lastly, we demonstrate in vivo
                      efficacy in an MRT PDX mouse model, in which single-agent
                      MLN4924 treatment significantly extends survival. Our study
                      demonstrates that organoids can be used to find drugs
                      selectively targeting tumor cells while leaving healthy
                      cells unharmed and proposes neddylation inhibition as a
                      therapeutic strategy in MRT.},
      keywords     = {MLN4924 (Other) / drug screening (Other) / malignant
                      rhabdoid tumors (Other) / neddylation (Other) / organoids
                      (Other) / targeted therapy (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / 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:34433038},
      doi          = {10.1016/j.celrep.2021.109568},
      url          = {https://inrepo02.dkfz.de/record/170414},
}