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@ARTICLE{Tomska:142146,
      author       = {K. Tomska$^*$ and R. Kurilov$^*$ and K. S. Lee$^*$ and J.
                      Hüllein$^*$ and M. Lukas$^*$ and L. Sellner and T.
                      Walther$^*$ and L. Wagner$^*$ and M. Oleś and B. Brors$^*$
                      and W. Huber and T. Zenz$^*$},
      title        = {{D}rug-based perturbation screen uncovers synergistic drug
                      combinations in {B}urkitt lymphoma.},
      journal      = {Scientific reports},
      volume       = {8},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2018-02376},
      pages        = {12046},
      year         = {2018},
      abstract     = {Burkitt lymphoma (BL) is a highly aggressive B-cell
                      lymphoma associated with MYC translocation. Here, we
                      describe drug response profiling of 42 blood cancer cell
                      lines including 17 BL to 32 drugs targeting key cancer
                      pathways and provide a systematic study of drug combinations
                      in BL cell lines. Based on drug response, we identified cell
                      line specific sensitivities, i.e. to venetoclax driven by
                      BCL2 overexpression and partitioned subsets of BL driven by
                      response to kinase inhibitors. In the combination screen,
                      including BET, BTK and PI3K inhibitors, we identified
                      synergistic combinations of PI3K and BTK inhibition with
                      drugs targeting Akt, mTOR, BET and doxorubicin. A detailed
                      comparison of PI3K and BTKi combinations identified subtle
                      differences, in line with convergent pathway activity. Most
                      synergistic combinations were identified for the BET
                      inhibitor OTX015, which showed synergistic effects for
                      $41\%$ of combinations including inhibitors of PI3K/AKT/mTOR
                      signalling. The strongest synergy was observed for the
                      combination of the CDK 2/7/9 inhibitor SNS032 and OTX015.
                      Our data provide a landscape of drug combination effects in
                      BL and suggest that targeting CDK and BET could provide a
                      novel vulnerability of BL.},
      cin          = {G200 / G100},
      ddc          = {600},
      cid          = {I:(DE-He78)G200-20160331 / I:(DE-He78)G100-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30104685},
      pmc          = {pmc:PMC6089937},
      doi          = {10.1038/s41598-018-30509-3},
      url          = {https://inrepo02.dkfz.de/record/142146},
}