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Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy

BACKGROUND: Paclitaxel 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 ear...

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Detalles Bibliográficos
Autores principales: Huehnchen, Petra, Schinke, Christian, Bangemann, Nikola, Dordevic, Adam D., Kern, Johannes, Maierhof, Smilla K., Hew, Lois, Nolte, Luca, Körtvelyessy, Peter, Göpfert, Jens C., Ruprecht, Klemens, Somps, Christopher J., Blohmer, Jens-Uwe, Sehouli, Jalid, Endres, Matthias, Boehmerle, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986065/
https://www.ncbi.nlm.nih.gov/pubmed/35133982
http://dx.doi.org/10.1172/jci.insight.154395
Descripción
Sumario:BACKGROUND: Paclitaxel 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. METHODS: NFL 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 (NFL(s)) concentrations were measured at both visits with single-molecule array technology. RESULTS: NFL was released from iPSC-DSNs upon paclitaxel incubation in a dose- and time-dependent manner and was inversely correlated with iPSC-DSN viability. NFL(s) 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 NFL(s) increase of +36 pg/mL from baseline was associated with a predicted CIPN probability of more than 0.5. CONCLUSION: NFL(s) was correlated with CIPN development and severity, which may guide neurotoxic chemotherapy in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT02753036. FUNDING: Deutsche 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.