%0 Journal Article
%A Huehnchen, Petra
%A Schinke, Christian
%A Bangemann, Nikola
%A Dordevic, Adam D
%A Kern, Johannes
%A Maierhof, Smilla K
%A Hew, Lois
%A Nolte, Luca
%A Körtvelyessy, Peter
%A Göpfert, Jens C
%A Ruprecht, Klemens
%A Somps, Christopher J
%A Blohmer, Jens-Uwe
%A Sehouli, Jalid
%A Endres, Matthias
%A Boehmerle, Wolfgang
%T Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy.
%J JCI insight
%V 7
%N 6
%@ 2379-3708
%C Ann Arbor, Michigan
%I JCI Insight
%M DZNE-2022-00474
%P e154395
%D 2022
%Z (CC BY)
%X 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
%K Antineoplastic Agents: adverse effects
%K Biomarkers
%K Cohort Studies
%K Humans
%K Neurofilament Proteins
%K Paclitaxel: adverse effects
%K Peripheral Nervous System Diseases: chemically induced
%K Peripheral Nervous System Diseases: diagnosis
%K Polyneuropathies: chemically induced
%K Polyneuropathies: diagnosis
%K Adult stem cells (Other)
%K Cancer (Other)
%K Neuroscience (Other)
%K Toxicology (Other)
%K Antineoplastic Agents (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%K Neurofilament Proteins (NLM Chemicals)
%K Paclitaxel (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35133982
%2 pmc:PMC8986065
%R 10.1172/jci.insight.154395
%U https://pub.dzne.de/record/163735