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@ARTICLE{ValdezCapuccino:290343,
      author       = {L. Valdez Capuccino and T. Kleitke and B. Szokol and L.
                      Svajda and F. Martin and F. Bonechi and M. Krekó and S.
                      Azami and A. Montinaro and Y. Wang and V. Nikolov and L.
                      Kaiser and D. Bonasera and J. Saggau and T. Scholz and A.
                      Schmitt and F. Beleggia and A. Reinhardt$^*$ and J. George
                      and G. Liccardi and H. Walczak and J. Tóvári and J.
                      Brägelmann and J. Montero and M. L. Sos$^*$ and L. Őrfi
                      and N. Peltzer},
      title        = {{CDK}9 inhibition as an effective therapy for small cell
                      lung cancer.},
      journal      = {Cell death $\&$ disease},
      volume       = {15},
      number       = {5},
      issn         = {2041-4889},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2024-01070},
      pages        = {345},
      year         = {2024},
      abstract     = {Treatment-naïve small cell lung cancer (SCLC) is typically
                      susceptible to standard-of-care chemotherapy consisting of
                      cisplatin and etoposide recently combined with PD-L1
                      inhibitors. Yet, in most cases, SCLC patients develop
                      resistance to first-line therapy and alternative therapies
                      are urgently required to overcome this resistance. In this
                      study, we tested the efficacy of dinaciclib, an FDA-orphan
                      drug and inhibitor of the cyclin-dependent kinase (CDK) 9,
                      among other CDKs, in SCLC. Furthermore, we report on a newly
                      developed, highly specific CDK9 inhibitor, VC-1, with
                      tumour-killing activity in SCLC. CDK9 inhibition displayed
                      high killing potential in a panel of mouse and human SCLC
                      cell lines. Mechanistically, CDK9 inhibition led to a
                      reduction in MCL-1 and cFLIP anti-apoptotic proteins and
                      killed cells, almost exclusively, by intrinsic apoptosis.
                      While CDK9 inhibition did not synergise with chemotherapy,
                      it displayed high efficacy in chemotherapy-resistant cells.
                      In vivo, CDK9 inhibition effectively reduced tumour growth
                      and improved survival in both autochthonous and syngeneic
                      SCLC models. Together, this study shows that CDK9 inhibition
                      is a promising therapeutic agent against SCLC and could be
                      applied to chemo-refractory or resistant SCLC.},
      keywords     = {Cyclin-Dependent Kinase 9: antagonists $\&$ inhibitors /
                      Cyclin-Dependent Kinase 9: metabolism / Small Cell Lung
                      Carcinoma: drug therapy / Small Cell Lung Carcinoma:
                      pathology / Humans / Animals / Lung Neoplasms: drug therapy
                      / Lung Neoplasms: pathology / Cell Line, Tumor / Mice /
                      Pyridinium Compounds: pharmacology / Pyridinium Compounds:
                      therapeutic use / Indolizines: pharmacology / Cyclic
                      N-Oxides: pharmacology / Apoptosis: drug effects / Bridged
                      Bicyclo Compounds, Heterocyclic: pharmacology / Bridged
                      Bicyclo Compounds, Heterocyclic: therapeutic use / Protein
                      Kinase Inhibitors: pharmacology / Protein Kinase Inhibitors:
                      therapeutic use / CDK9 protein, human (NLM Chemicals) /
                      dinaciclib (NLM Chemicals)},
      cin          = {ED01 / MU01},
      ddc          = {570},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38769311},
      doi          = {10.1038/s41419-024-06724-4},
      url          = {https://inrepo02.dkfz.de/record/290343},
}