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@ARTICLE{Huehnchen:163735,
      author       = {Huehnchen, Petra and Schinke, Christian and Bangemann,
                      Nikola and Dordevic, Adam D and Kern, Johannes and Maierhof,
                      Smilla K and Hew, Lois and Nolte, Luca and Körtvelyessy,
                      Peter and Göpfert, Jens C and Ruprecht, Klemens and Somps,
                      Christopher J and Blohmer, Jens-Uwe and Sehouli, Jalid and
                      Endres, Matthias and Boehmerle, Wolfgang},
      title        = {{N}eurofilament proteins as a potential biomarker in
                      chemotherapy-induced polyneuropathy.},
      journal      = {JCI insight},
      volume       = {7},
      number       = {6},
      issn         = {2379-3708},
      address      = {Ann Arbor, Michigan},
      publisher    = {JCI Insight},
      reportid     = {DZNE-2022-00474},
      pages        = {e154395},
      year         = {2022},
      note         = {(CC BY)},
      abstract     = {BACKGROUNDPaclitaxel chemotherapy frequently induces
                      dose-limiting sensory axonal polyneuropathy. Given that
                      sensory symptoms are challenging to assess objectively in
                      clinical practice, an easily accessible biomarker for
                      chemotherapy-induced polyneuropathy (CIPN) holds the
                      potential to improve early diagnosis. Here, we describe
                      neurofilament light chain (NFL), a marker for neuroaxonal
                      damage, as a translational surrogate marker for
                      CIPN.METHODSNFL concentrations were measured in an in vitro
                      model of CIPN, exposing induced pluripotent stem
                      cell-derived sensory neurons (iPSC-DSNs) to paclitaxel.
                      Patients with breast or ovarian cancer undergoing paclitaxel
                      chemotherapy, breast cancer control patients without
                      chemotherapy, and healthy controls were recruited in a
                      cohort study and examined before chemotherapy (V1) and after
                      28 weeks (V2, after chemotherapy). CIPN was assessed by the
                      validated Total Neuropathy Score reduced (TNSr), which
                      combines patient-reported symptoms with data from clinical
                      examinations. Serum NFL (NFLs) concentrations were measured
                      at both visits with single-molecule array
                      technology.RESULTSNFL was released from iPSC-DSNs upon
                      paclitaxel incubation in a dose- and time-dependent manner
                      and was inversely correlated with iPSC-DSN viability. NFLs
                      strongly increased in paclitaxel-treated patients with CIPN,
                      but not in patients receiving chemotherapy without CIPN or
                      controls, resulting in an $86\%$ sensitivity and $87\%$
                      specificity. An NFLs increase of +36 pg/mL from baseline was
                      associated with a predicted CIPN probability of more than
                      0.5.CONCLUSIONNFLs was correlated with CIPN development and
                      severity, which may guide neurotoxic chemotherapy in the
                      future.TRIAL REGISTRATIONClinicalTrials.gov
                      NCT02753036.FUNDINGDeutsche Forschungsgemeinschaft (EXC 257
                      NeuroCure), BMBF (Center for Stroke Research Berlin, 01 EO
                      0801), Animalfree Research, EU Horizon 2020 Innovative
                      Medicines Initiative 2 Joint Undertaking (TransBioLine,
                      821283), Charité 3R - Replace - Reduce - Refine.},
      keywords     = {Antineoplastic Agents: adverse effects / Biomarkers /
                      Cohort Studies / Humans / Neurofilament Proteins /
                      Paclitaxel: adverse effects / Peripheral Nervous System
                      Diseases: chemically induced / Peripheral Nervous System
                      Diseases: diagnosis / Polyneuropathies: chemically induced /
                      Polyneuropathies: diagnosis / Adult stem cells (Other) /
                      Cancer (Other) / Neuroscience (Other) / Toxicology (Other) /
                      Antineoplastic Agents (NLM Chemicals) / Biomarkers (NLM
                      Chemicals) / Neurofilament Proteins (NLM Chemicals) /
                      Paclitaxel (NLM Chemicals)},
      cin          = {AG Düzel 3 / AG Endres},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006 / I:(DE-2719)1811005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35133982},
      pmc          = {pmc:PMC8986065},
      doi          = {10.1172/jci.insight.154395},
      url          = {https://pub.dzne.de/record/163735},
}