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@ARTICLE{Jones:144388,
      author       = {D. Jones$^*$ and A. Banito$^*$ and T. G. P. Grünewald and
                      M. Haber and N. Jäger$^*$ and M. Kool$^*$ and T. Milde$^*$
                      and J. J. Molenaar and A. Nabbi and T. J. Pugh and G.
                      Schleiermacher and M. A. Smith and F. Westermann$^*$ and S.
                      Pfister$^*$},
      title        = {{M}olecular characteristics and therapeutic vulnerabilities
                      across paediatric solid tumours.},
      journal      = {Nature reviews / Cancer Cancer [...]},
      volume       = {19},
      number       = {8},
      issn         = {1474-1768},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2019-01841},
      pages        = {420 - 438},
      year         = {2019},
      abstract     = {The spectrum of tumours arising in childhood is
                      fundamentally different from that seen in adults, and they
                      are known to be divergent from adult malignancies in terms
                      of cellular origins, epidemiology, genetic complexity,
                      driver mutations and underlying mutational processes.
                      Despite the immense knowledge generated through sequencing
                      efforts and functional characterization of identified
                      (epi-)genetic alterations over the past decade, the clinical
                      implications of this knowledge have so far been limited.
                      Novel preclinical platforms such as the European Innovative
                      Therapies for Children with Cancer-Paediatric Preclinical
                      Proof-of-Concept Platform and the US-based Pediatric
                      Preclinical Testing Consortium are being developed to try to
                      change this by aiming to recapitulate the extensive
                      heterogeneity of paediatric tumours and thereby, hopefully,
                      improve the ability to predict clinical benefit. Numerous
                      studies have also been established worldwide to provide
                      patients with access to real-time molecular profiling and
                      the possibility of more precise mechanism-of-action-based
                      treatments. In addition to tumour-intrinsic findings and
                      mechanisms, ongoing studies are investigating features such
                      as the immune microenvironment of paediatric tumours in
                      comparison with adult cancers - currently of very timely
                      clinical relevance. However, there is an ongoing need for
                      rigorous preclinical biomarker and target validation to feed
                      into the next generation of molecularly stratified clinical
                      trials. This Review aims to provide a comprehensive
                      state-of-the-art overview of the molecular landscape of
                      paediatric solid tumours, including their underlying genomic
                      alterations and interactions with the microenvironment,
                      complemented with our current understanding of potential
                      therapeutic vulnerabilities and how these can be
                      preclinically tested using more accurate predictive methods.
                      Finally, we provide an outlook on the challenges and
                      opportunities associated with translating this overwhelming
                      scientific progress into real clinical benefit.},
      subtyp        = {Review Article},
      cin          = {B360 / B380 / B062 / B310 / B087},
      ddc          = {610},
      cid          = {I:(DE-He78)B360-20160331 / I:(DE-He78)B380-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B310-20160331 /
                      I:(DE-He78)B087-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31300807},
      doi          = {10.1038/s41568-019-0169-x},
      url          = {https://inrepo02.dkfz.de/record/144388},
}