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@ARTICLE{Pauck:298952,
      author       = {D. Pauck$^*$ and D. J. Picard$^*$ and M. Maue$^*$ and K.
                      Taban$^*$ and V. Marquardt$^*$ and L. Blümel$^*$ and J.
                      Bartl$^*$ and N. Qin and N. Kubon$^*$ and D. Schöndorf and
                      F.-D. Meyer$^*$ and J. Theruvath and S. Mitra and M.
                      Hasselblatt and M. C. Frühwald and G. Reifenberger$^*$ and
                      M. Remke$^*$},
      title        = {{A}n in vitro pharmacogenomic approach reveals
                      subtype-specific therapeutic vulnerabilities in atypical
                      teratoid/rhabdoid tumors ({AT}/{RT}).},
      journal      = {Pharmacological research},
      volume       = {213},
      issn         = {1043-6618},
      address      = {London},
      publisher    = {Academic Press},
      reportid     = {DKFZ-2025-00386},
      pages        = {107660},
      year         = {2025},
      note         = {Volume 213, March 2025, 107660},
      abstract     = {Atypical teratoid/rhabdoid tumor (AT/RT) is a highly
                      malignant embryonal brain tumor driven by genetic
                      alterations inactivating the SMARCB1 or, less commonly, the
                      SMARCA4 gene. Large-scale molecular profiling studies have
                      identified distinct molecular subtypes termed AT/RT-TYR,
                      -SHH and -MYC. Despite the increasing knowledge of AT/RT
                      biology, curative treatment options are still lacking for
                      certain risk groups and outcomes of these patients remain
                      poor. We performed an in vitro high-throughput drug screen
                      of 768 small molecule drugs covering conventional
                      chemotherapeutic agents and late-stage developmental drugs
                      in 13 AT/RT cell lines and determined intra- and
                      inter-entity differential responses to unravel specific
                      vulnerabilities. Our data demonstrated in vitro preferential
                      activity of mitogen-activated protein kinase kinase (MEK)
                      and mouse double minute 2 homolog (MDM2) inhibitors in AT/RT
                      cell lines compared to other high-grade brain tumor cell
                      lines including medulloblastoma and malignant glioma models.
                      Moreover, we were able to link distinct drug response
                      patterns to AT/RT molecular subtypes through integration of
                      drug response data with large-scale DNA methylation and
                      RNASeq-based expression profiles. Subtype-dependent drug
                      response profiles demonstrated sensitivity of AT/RT-SHH cell
                      lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90
                      (HSP90) inhibitors, and increased activity of microtubule
                      inhibitors, kinesin spindle protein (KSP) inhibitors, and
                      the eukaryotic translation initiation factor 4E (eIF4E)
                      inhibitor briciclib in a subset of AT/RT-MYC cell lines. In
                      summary, our in vitro pharmacogenomic approach revealed
                      preclinical evidence of tumor type- and subtype-specific
                      therapeutic vulnerabilities in AT/RT cell lines that may
                      inform future in vivo and clinical evaluations of novel
                      pharmacological strategies.},
      keywords     = {17-AAG/Tanespimycin (PubChem CID: 6505803) (Other) /
                      ABT-199/Venetoclax (PubChem CID: 49846579) (Other) / ABT-737
                      (PubChem CID: 11228183) (Other) / Atypical teratoid/rhabdoid
                      tumor (Other) / DNA methylation profiling (Other) / GDC-0623
                      (PubChem CID: 42642654) (Other) / RNA sequencing (Other) /
                      briciclib (PubChem CID: 11248490) (Other) / high-throughput
                      drug screening (Other) / idasanutlin (PubChem CID: 53358942)
                      (Other) / ombrabulin hydrochloride (PubChem CID: 6918404)
                      (Other) / targeted therapy (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39961404},
      doi          = {10.1016/j.phrs.2025.107660},
      url          = {https://inrepo02.dkfz.de/record/298952},
}