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@ARTICLE{Rieke:277441,
      author       = {D. Rieke$^*$ and S. Schröder and P. Schafhausen and E.
                      Blanc and E. Zuljan and B. von der Emde and D. Beule and U.
                      Keller$^*$ and U. Keilholz$^*$ and K. Klinghammer$^*$},
      title        = {{T}argeted treatment in a case series of {AR}+,
                      {HRAS}/{PIK}3{CA} co-mutated salivary duct carcinoma.},
      journal      = {Frontiers in oncology},
      volume       = {13},
      issn         = {2234-943X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01378},
      pages        = {1107134},
      year         = {2023},
      abstract     = {A subgroup of salivary duct carcinoma (SDC) harbor
                      overexpression of the androgen receptor (AR), and
                      co-occurring mutations in the HRAS- and PIK3CA-genes. The
                      impact of genomic complexity on targeted treatment
                      strategies in advanced cancer is unknown.We analyzed
                      molecular and clinical data from an institutional molecular
                      tumor board (MTB) to identify AR+, HRAS/PIK3CA co-mutated
                      SDC. Follow-up was performed within the MTB registrational
                      study or retrospective chart review after approval by the
                      local ethics committee. Response was assessed by the
                      investigator. A systematic literature search was performed
                      in MEDLINE to identify additional clinically annotated
                      cases.4 patients with AR+ HRAS/PIK3CA co-mutated SDC and
                      clinical follow-up data were identified from the MTB. An
                      additional 9 patients with clinical follow-up were
                      identified from the literature. In addition to AR
                      overexpression and HRAS and PIK3CA-alterations, PD-L1
                      expression and Tumor Mutational Burden > 10 Mutations per
                      Megabase were identified as additional potentially
                      targetable alterations. Among evaluable patients, androgen
                      deprivation therapy (ADT) was initiated in 7 patients (1
                      Partial Response (PR), 2 Stable Disease (SD), 3 Progressive
                      Disease (PD), 2 not evaluable), tipifarnib was initiated in
                      6 patients (1 PR, 4 SD, 1 PD). One patient each was treated
                      with immune checkpoint inhibition (Mixed Response) and
                      combination therapies of tipifarnib and ADT (SD) and
                      alpelisib and ADT (PR).Available data further support
                      comprehensive molecular profiling of SDC. Combination
                      therapies, PI3K-inhibitors and immune therapy warrant
                      further investigation, ideally in clinical trials. Future
                      research should consider this rare subgroup of SDC.},
      keywords     = {head and neck cancer (Other) / molecular tumor board
                      (Other) / precision oncology (Other) / salivary duct
                      carcinoma (Other) / salivary gland cancer (Other) / targeted
                      therapy (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37427101},
      pmc          = {pmc:PMC10325704},
      doi          = {10.3389/fonc.2023.1107134},
      url          = {https://inrepo02.dkfz.de/record/277441},
}