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@ARTICLE{Keller:275260,
      author       = {K. M. Keller and J. Koetsier and L. Schild and V. Amo-Addae
                      and S. Eising and K. van den Handel and K. Ober and B.
                      Koopmans and A. Essing and M. L. van den Boogaard and K. P.
                      S. Langenberg and N. Jäger$^*$ and M. Kool$^*$ and S.
                      Pfister$^*$ and M. E. M. Dolman and J. J. Molenaar and S. R.
                      van Hooff},
      title        = {{T}he potential of {PARP} as a therapeutic target across
                      pediatric solid malignancies.},
      journal      = {BMC cancer},
      volume       = {23},
      number       = {1},
      issn         = {1471-2407},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2023-00707},
      pages        = {310},
      year         = {2023},
      abstract     = {Pediatric cancer is the leading cause of disease-related
                      death in children and the need for better therapeutic
                      options remains urgent. Due to the limited number of
                      patients, target and drug development for pediatrics is
                      often supplemented by data from studies focused on adult
                      cancers. Recent evidence shows that pediatric cancers
                      possess different vulnerabilities that should be explored
                      independently from adult cancers.Using the publicly
                      available Genomics of Drug Sensitivity in Cancer database,
                      we explore therapeutic targets and biomarkers specific to
                      the pediatric solid malignancies Ewing sarcoma,
                      medulloblastoma, neuroblastoma, osteosarcoma, and
                      rhabdomyosarcoma. Results are validated using cell viability
                      assays and high-throughput drug screens are used to identify
                      synergistic combinations.Using published drug screening
                      data, PARP is identified as a drug target of interest across
                      multiple different pediatric malignancies. We validate these
                      findings, and we show that efficacy can be improved when
                      combined with conventional chemotherapeutics, namely
                      topoisomerase inhibitors. Additionally, using gene set
                      enrichment analysis, we identify ribosome biogenesis as a
                      potential biomarker for PARP inhibition in pediatric cancer
                      cell lines.Collectively, our results provide evidence to
                      support the further development of PARP inhibition and the
                      combination with TOP1 inhibition as a therapeutic approach
                      in solid pediatric malignancies. Additionally, we propose
                      ribosome biogenesis as a component to PARP inhibitor
                      sensitivity that should be further investigated to help
                      maximize the potential utility of PARP inhibition and
                      combinations across pediatric solid malignancies.},
      keywords     = {DNA damage (Other) / PARP (Other) / Pediatric cancer
                      (Other) / Replication stress (Other) / Ribosomes (Other) /
                      Synergy (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:37020198},
      doi          = {10.1186/s12885-022-10319-7},
      url          = {https://inrepo02.dkfz.de/record/275260},
}