% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kuhn:186734,
      author       = {C. Kuhn and M. Boeschen and M. Philip$^*$ and T.
                      Schöneberg and D. Thor and S. Horn$^*$},
      title        = {{C}andidate drugs associated with sensitivity of cancer
                      cell lines with {DLST} amplification or high m{RNA} levels.},
      journal      = {OncoTarget},
      volume       = {14},
      number       = {1},
      issn         = {1949-2553},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2023-00086},
      pages        = {14-20},
      year         = {2023},
      abstract     = {Overexpression of the dihydrolipoamide
                      S-succinyltransferase (DLST) is associated with poor outcome
                      in neuroblastoma patients and triple-negative breast cancer
                      (TNBC) and specifically with the oxidative phosphorylation
                      (OXPHOS) pathway. Inhibitors of OXPHOS were previously
                      suggested as a potential therapeutic strategy for a subset
                      of patients with high-risk neuroblastoma. Here, we tested if
                      cell lines with DLST amplifications or high mRNA levels were
                      associated with sensitivity to 250 drugs from the Genomics
                      of Drug Sensitivity in Cancer (GDSC) dataset by comparing
                      them to cell lines without these changes. DLST-altered cell
                      lines were more sensitive to 7 approved drugs, among these
                      obatoclax mesylate, a BCL2 inhibitor that reduces OXPHOS in
                      human leukemia stem cells. Moreover, several protein kinase
                      inhibitors were identified to be efficient in cell lines
                      with DLST amplifications or high mRNA levels, suggesting a
                      vulnerability of DLST-altered cell lines for drugs targeting
                      the ERK/MAPK pathway. Furthermore, increased DLST expression
                      in cell lines with driver mutations in KRAS supported this
                      relationship. We therefore conclude that, in addition to
                      OXPHOS, protein kinases could be potential targets of
                      therapy in the presence of DLST amplifications or high mRNA
                      levels. The new drug candidates proposed here could serve in
                      experimental testing on drug efficacy in knock-in cell lines
                      and DLST-activated tumors.},
      keywords     = {DLST (Other) / drug repurposing (Other) / drug resistance
                      (Other) / drug sensitivity (Other) / neuroblastoma (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:36634214},
      doi          = {10.18632/oncotarget.28342},
      url          = {https://inrepo02.dkfz.de/record/186734},
}