TY  - JOUR
AU  - Huehnchen, Petra
AU  - Schinke, Christian
AU  - Bangemann, Nikola
AU  - Dordevic, Adam D
AU  - Kern, Johannes
AU  - Maierhof, Smilla K
AU  - Hew, Lois
AU  - Nolte, Luca
AU  - Körtvelyessy, Peter
AU  - Göpfert, Jens C
AU  - Ruprecht, Klemens
AU  - Somps, Christopher J
AU  - Blohmer, Jens-Uwe
AU  - Sehouli, Jalid
AU  - Endres, Matthias
AU  - Boehmerle, Wolfgang
TI  - Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy.
JO  - JCI insight
VL  - 7
IS  - 6
SN  - 2379-3708
CY  - Ann Arbor, Michigan
PB  - JCI Insight
M1  - DZNE-2022-00474
SP  - e154395
PY  - 2022
N1  - (CC BY)
AB  - 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
KW  - Antineoplastic Agents: adverse effects
KW  - Biomarkers
KW  - Cohort Studies
KW  - Humans
KW  - Neurofilament Proteins
KW  - Paclitaxel: adverse effects
KW  - Peripheral Nervous System Diseases: chemically induced
KW  - Peripheral Nervous System Diseases: diagnosis
KW  - Polyneuropathies: chemically induced
KW  - Polyneuropathies: diagnosis
KW  - Adult stem cells (Other)
KW  - Cancer (Other)
KW  - Neuroscience (Other)
KW  - Toxicology (Other)
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Paclitaxel (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35133982
C2  - pmc:PMC8986065
DO  - DOI:10.1172/jci.insight.154395
UR  - https://pub.dzne.de/record/163735
ER  -