% 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{Seiboldt:291417,
      author       = {T. Seiboldt$^*$ and C. Zeiser$^*$ and D. Nguyen$^*$ and S.
                      Celikyürekli$^*$ and S. Herter$^*$ and S. Najafi$^*$ and A.
                      Stroh-Dege$^*$ and C. Meulenbroeks and N. Mack$^*$ and R.
                      Salem-Altintas$^*$ and F. Westermann$^*$ and M.
                      Schlesner$^*$ and T. Milde$^*$ and M. Kool$^*$ and T.
                      Holland-Letz$^*$ and M. Vogler$^*$ and H. Peterziel$^*$ and
                      O. Witt$^*$ and I. Oehme$^*$},
      title        = {{S}ynergy of retinoic acid and {BH}3 mimetics in
                      {MYC}({N})-driven embryonal nervous system tumours.},
      journal      = {British journal of cancer},
      volume       = {131},
      number       = {4},
      issn         = {0007-0920},
      address      = {Edinburgh},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2024-01391},
      pages        = {763-777},
      year         = {2024},
      note         = {#EA:B310#LA:B310# / 2024 Sep;131(4):763-777},
      abstract     = {Certain paediatric nervous system malignancies have dismal
                      prognoses. Retinoic acid (RA) is used in neuroblastoma
                      treatment, and preclinical data indicate potential benefit
                      in selected paediatric brain tumour entities. However,
                      limited single-agent efficacy necessitates combination
                      treatment approaches.We performed drug sensitivity profiling
                      of 76 clinically relevant drugs in combination with RA in 16
                      models (including patient-derived tumouroids) of the most
                      common paediatric nervous system tumours. Drug responses
                      were assessed by viability assays, high-content imaging, and
                      apoptosis assays and RA relevant pathways by RNAseq from
                      treated models and patient samples obtained through the
                      precision oncology programme INFORM (n = 2288).
                      Immunoprecipitation detected BCL-2 family interactions, and
                      zebrafish embryo xenografts were used for in vivo efficacy
                      testing.Group 3 medulloblastoma (MBG3) and neuroblastoma
                      models were highly sensitive to RA treatment. RA induced
                      differentiation and regulated apoptotic genes. RNAseq
                      analysis revealed high expression of BCL2L1 in MBG3 and BCL2
                      in neuroblastomas. Co-treatments with RA and BCL-2/XL
                      inhibitor navitoclax synergistically decreased viability at
                      clinically achievable concentrations. The combination of RA
                      with navitoclax disrupted the binding of BIM to BCL-XL in
                      MBG3 and to BCL-2 in neuroblastoma, inducing apoptosis in
                      vitro and in vivo.RA treatment primes MBG3 and NB cells for
                      apoptosis, triggered by navitoclax cotreatment.},
      cin          = {B310 / HD01 / W610 / B062 / B087 / C060 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)W610-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B087-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)FM01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38942989},
      doi          = {10.1038/s41416-024-02740-5},
      url          = {https://inrepo02.dkfz.de/record/291417},
}