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@ARTICLE{Gatz:307659,
      author       = {S. A. Gatz and J. Glade-Bender and A. D. J. Pearson and M.
                      V. Ortiz and R. Bernardi and L. Chesler and S. Clifford and
                      S. Cohen-Gogo and E. De La Cuesta and T. de Rojas and K.
                      Durinck and S. Federico and E. Fox and S. George and I.
                      Gounaris and A. G. Henssen and M. Irwin and M. Kool$^*$ and
                      A. Lau and K. Nysom and A. Pappo and G. K. Pennock and S. M.
                      Pfister$^*$ and N. Scobie and E. K. Slotkin and M. Smith and
                      F. Speleman and E. A. Stewart and B. J. Weigel and G.
                      Vassal},
      title        = {{P}athway for the {D}evelopment of {ATR} {I}nhibitors in
                      {P}ediatric {M}alignancies: {A}n {ACCELERATE}
                      {M}ultistakeholder {A}nalysis.},
      journal      = {JCO precision oncology},
      volume       = {10},
      number       = {10},
      issn         = {2473-4284},
      address      = {Alexandria, VA},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2026-00116},
      pages        = {e2500642},
      year         = {2026},
      note         = {#NCTZFB26# / #DKTKZFB26#},
      abstract     = {High levels of DNA replication stress and defects in the
                      DNA damage response (DDR) pathways are vulnerabilities of
                      many poor prognosis childhood malignancies. Ataxia
                      telangiectasia and Rad3-related protein (ATR) is a key
                      regulator of these pathways and constitutes an attractive
                      target, especially in combination. However, the malignancies
                      where ATR inhibitors have maximum benefit and synergistic
                      combinations differ between adults and children.ACCELERATE
                      convened a multistakeholder meeting and conducted review and
                      analysis to propose the optimal pathway for the development
                      of ATR inhibitors in pediatric malignancies.Considering the
                      lack of identified biomarkers, the initial evaluation of ATR
                      inhibitors should focus on Ewing sarcoma, rhabdomyosarcoma,
                      and neuroblastoma in view of their high levels of DNA
                      replication stress and defects in DDR pathways. Early phase
                      trials of ATR inhibitors should be iterative, based on a
                      clear hypothesis with responders and nonresponders
                      undergoing detailed molecular analysis and a revised new
                      hypothesis generated. Trial designs should restrict
                      monotherapy evaluation to a brief exposure in a small number
                      of patients and progress rapidly to combinations.
                      Highlighted combination partners are poly(ADP-ribose)
                      polymerase inhibitors and antibody drug conjugates with
                      topoisomerase I inhibitor payloads. Combinations with ALK
                      inhibitors (in ALK/MYCN-aberrant neuroblastoma) and aurora A
                      kinase (in MYCN-amplified) are supported by robust
                      mechanisms of action and preclinical data. Early
                      interactions with regulators are crucial, and early phase
                      clinical trials should be conducted in regulatory-approved,
                      academic-sponsored, industry-supported, platform trials.ATR
                      inhibitors are a prototype for the development of medicinal
                      products in a limited pediatric population. For the
                      substantial potential of ATR inhibitors in children with
                      malignancy to be realized, strategic planning between
                      academia, industry, regulators, and patient advocates is
                      vital.},
      subtyp        = {Review Article},
      keywords     = {Humans / Ataxia Telangiectasia Mutated Proteins:
                      antagonists $\&$ inhibitors / Child / Neoplasms: drug
                      therapy / Neuroblastoma: drug therapy / Sarcoma, Ewing: drug
                      therapy / Protein Kinase Inhibitors: therapeutic use /
                      Protein Kinase Inhibitors: pharmacology / Ataxia
                      Telangiectasia Mutated Proteins (NLM Chemicals) / ATR
                      protein, human (NLM Chemicals) / Protein Kinase Inhibitors
                      (NLM Chemicals)},
      cin          = {B062 / HD01 / HD02},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)HD02-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41538758},
      doi          = {10.1200/PO-25-00642},
      url          = {https://inrepo02.dkfz.de/record/307659},
}