Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy

Sumitani, Masahiko; Ogata, Toru; Natori, Akina; Hozumi, Jun; Shimojo, Nobutake; Kida, Kumiko; Yamauchi, Hideko; Yamauchi, Teruo

doi:10.3892/br.2016.648

Cited by 10 publications

(15 citation statements)

References 9 publications

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“…Approximately one‐half of these studies (45 preclinical studies) focused on taxane‐based chemotherapies only or in combination with other agents, with the majority of these studies investigating paclitaxel 23‐60 and only 2 studies investigating docetaxel 61,62 . The second most common chemotherapy studies were platinum‐based compounds, with more studies investigating oxaliplatin 23,24,31,34,35,39,62‐72 than cisplatin 26,35,40,49,73‐82 . Studies less often involved bortezomib 24,26,67,83‐94 and vincristine 42,45,50,54,84,93,95‐101 .…”

Section: Resultsmentioning

confidence: 99%

“…Among the clinical studies (12%), the majority (8 clinical studies) included taxane‐based therapies 36,39,40,45,49,61,62,102 . Other therapies included vincristine, 45,84,93 cisplatin, 40,49 oxaliplatin, 39,61 bortezomib, 84,93 and thalidomide 84,93 .…”

Section: Resultsmentioning

confidence: 99%

“…Other therapies included vincristine, 45,84,93 cisplatin, 40,49 oxaliplatin, 39,61 bortezomib, 84,93 and thalidomide 84,93 . Two of these studies explored inflammation‐related biomarkers, 36,39 and other studies examined mechanisms related to neuropathy such as nerve growth factor, 40,93 epidermal nerve fibers, 45,61 and axonal damage 40,62 . These studies using human subjects involved collecting blood samples or observing the brain scans of patients, including those within certain subgroups such as patients with lung cancer, 40 multiple myeloma, 84 breast cancer, 36,49 or hematologic cancer 93 .…”

Section: Resultsmentioning

confidence: 99%

“…For example, only studies involving paclitaxel, vincristine, and bortezomib suggested microtubule stabilization as a mechanism for CIPN 38,43,46,57,87,91,95 . Table 2 23‐115 provides an overview of each type of mechanism studied categorized by the type of chemotherapy.…”

Section: Resultsmentioning

confidence: 99%

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Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

Germain

O’Mara

Robinson

et al. 2020

Cancer

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BACKGROUND: To the authors' knowledge, the empiric identification of agents and interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN) has resulted in only 1 agent that modestly mitigates it and no agents or interventions that prevent its development. This speaks to the need for a mechanistic understanding of CIPN to develop effective interventions. METHODS: To understand the extent to which mechanistic understanding of CIPN is being translated into the development of interventions, the National Cancer Institute conducted a review of the National Institutes of Health (NIH)'s portfolio of investigator-initiated grants, the literature regarding CIPN mechanisms, and the clinical trials listed in the ClinicalTrials.gov database from January 1, 2011, to May 22, 2019. RESULTS: A total of 69 NIH-supported grants and 95 published articles were identified that evaluated mechanistic pathways of 7 different chemotherapy agents that cause CIPN. The review also identified 35 clinical trials that investigated agents or devices with which to treat CIPN. Only 3 trials incorporated a mechanistic rationale to support the choice of the intervention. CONCLUSIONS: To the authors' knowledge, very little of the mechanistic understanding of the development of CIPN is being translated into intervention rationale in clinical trials that evaluate interventions to mitigate CIPN. Efforts to incentivize this translation are needed. Cancer 2020;126:4602-4613.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

Germain

O’Mara

Robinson

et al. 2020

Cancer

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“…22 Moreover, sNfL levels allow the early identification of axonopathy and have also shown to be a marker that is correlated with the final CIPN severity, mostly in paclitaxel rather than in cisplatin-treated animals. 22 However, two subsequent clinical studies have led to conflicting results, one against 23 and one in favor of the use of NfL as markers of CIPN in the clinical setting. 24 Enhanced pathogenetic approaches, with the use of biomarkers, derived from easily accessible biological testing, are warranted to identify potential druggable therapeutic targets in the PIPN setting.…”

Section: Introductionmentioning

confidence: 99%

Prospectively assessing serum neurofilament light chain levels as a biomarker of paclitaxel‐induced peripheral neurotoxicity in breast cancer patients

Karteri

Bruna

Mariotto

et al. 2022

J Peripheral Nervous Sys

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Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as a biomarker of paclitaxel‐induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12‐weekly paclitaxel‐based regimen. Patients were clinically examined by means of the Total Neuropathy Score‐clinical version (TNSc), while sNfL were quantified, using the highly sensitive Simoa technique, before starting chemotherapy (baseline), after 2 (week 2) and 3 (week 3) weekly courses, and at the end of chemotherapy (week 12). Among 59 included patients (mean age: 53.1 ± 11.5 years), 33 (56%) developed grade 0‐1 and 26 (44%) grade 2‐3 PIPN at week 12. A significant longitudinal increase of sNfL levels from baseline to week‐12 was determined, whereas patients with TNSc grade 2‐3 PIPN had significantly increased sNfL levels at week 12, compared to those with grade 0‐1. receiver‐operated characteristics (ROC) analysis defined a value of NfL of >85 pg/mL at week 3 as the best discriminative determination to predict the development of grade 2‐3 PIPN at week 12 (sensitivity 46.2%, specificity 84.8%). The logistic binary regression analysis revealed that age > 50 years and the cutoff of >85 pg/mL of sNfL levels at week 3 independently predicted the development of grade 2‐3 PIPN at week 12 with a sensitivity of 46%, a specificity of 91%, and a positive and negative predictive values of 75% and 67%, respectively. sNfL levels seem to be a valuable biomarker of neuro‐axonal injury in PIPN. An early increase of this biomarker after a 3‐weekly chemotherapy course can be a predictive marker of final PIPN severity.

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Different genes may be involved in distal and local sensitization: A genome‐wide gene‐based association study and meta‐analysis

Kouraki

Doherty

Fernandes

et al. 2022

European Journal of Pain

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Background Neuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic‐like pain phenotypes could be clinically important in identifying targets for early intervention. Methods We performed a genome‐wide gene‐based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain‐free sites (anterior tibia), a measure of distal sensitization, and from proximal pain‐affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort. We next performed gene‐based fixed‐effects meta‐analysis of PPTs and a neuropathic‐like pain phenotype using genome‐wide association study (GWAS) data from KPIC and from an independent cohort of 613 post‐TJR participants, respectively. Results The most significant genes associated with distal and local sensitization were OR5B3 and BRDT, respectively. We also found previously identified neuropathic pain‐associated genes—KCNA1, MTOR, ADORA1 and SCN3B—associated with PPT at the anterior tibia and an inflammatory pain gene—PTAFR—associated with PPT at the lateral joint line. Meta‐analysis results of anterior tibia and neuropathic‐like pain phenotypes revealed genes associated with bone morphogenesis, neuro‐inflammation, obesity, type 2 diabetes, cardiovascular disease and cognitive function. Conclusions Overall, our results suggest that different biological processes might be involved in distal and local sensitization, and common genetic mechanisms might be implicated in distal sensitization and neuropathic‐like pain. Future studies are needed to replicate these findings. Significance To the best of our knowledge, this is the first GWAS for pain sensitization and the first gene‐based meta‐analysis of pain sensitization and neuropathic‐like pain. Higher pain sensitization and neuropathic pain symptoms are associated with persistent pain after surgery hence, identifying genetic biomarkers and molecular pathways associated with these traits is clinically relevant.

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Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy

Cited by 10 publications

References 9 publications

Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

Prospectively assessing serum neurofilament light chain levels as a biomarker of paclitaxel‐induced peripheral neurotoxicity in breast cancer patients

Different genes may be involved in distal and local sensitization: A genome‐wide gene‐based association study and meta‐analysis

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