Chemotherapy-induced peripheral neuropathy: emerging roles of metabolic reprogramming, signal sensing, and epigenetic plasticity

{"Chemotherapy-induced":[0],"peripheral":[1],"neuropathy":[2,87],"(CIPN)":[3],"is":[4,115],"one":[5],"of":[6,14,55,62,79,103,113,142,192,213,300],"the":[7,53,60,109,140,189,211,289,298],"most":[8],"common":[9],"and":[10,24,29,33,47,66,81,111,136,173,183,203,242,257,268,282,295],"persistent":[11],"adverse":[12],"effects":[13],"cancer":[15],"treatment,":[16],"particularly":[17],"associated":[18,199],"with":[19,52,200,238,245],"platinum-based":[20],"compounds":[21],"(e.g.,":[22,27,161],"oxaliplatin":[23],"cisplatin),":[25],"taxanes":[26],"paclitaxel":[28],"docetaxel),":[30],"vinca":[31],"alkaloids,":[32],"proteasome":[34],"inhibitors.":[35],"Traditional":[36],"studies":[37],"have":[38,88],"linked":[39],"its":[40],"development":[41,267,299],"to":[42,70,108,188,233],"microtubule":[43],"damage,":[44],"mitochondrial":[45],"dysfunction,":[46],"ion":[48],"channel":[49],"abnormalities.":[50],"However,":[51],"advancement":[54],"metabolomics":[56],"in":[57,85,146,171,288],"recent":[58],"years,":[59],"contribution":[61],"systemic":[63,235],"metabolic":[64,125,144,149,167,236,252,278],"remodeling":[65],"gut":[67],"microbiota-derived":[68],"metabolites":[69,80,106],"CIPN":[71,114,266],"pathogenesis":[72],"has":[73],"become":[74,89],"increasingly":[75,90],"recognized.":[76],"The":[77],"role":[78],"their":[82,93,158],"corresponding":[83],"receptors":[84,160],"regulating":[86,196],"recognized,":[91],"including":[92],"impact":[94],"on":[95,123,128,220],"epigenetic":[96,177,229,258,283],"modifications.":[97],"To":[98],"date,":[99],"a":[100,206,225,261],"comprehensive":[101],"understanding":[102,265],"how":[104,154],"various":[105],"contribute":[107,187],"onset":[110],"persistence":[112,191],"still":[116],"lacking.":[117],"This":[118,248],"review":[119],"synthesizes":[120],"current":[121],"evidence":[122],"chemotherapy-induced":[124,251],"reprogramming,":[126],"focusing":[127],"bile":[129],"acids,":[130,133,135],"short-chain":[131],"fatty":[132],"amino":[134,320],"lipids,":[137],"while":[138],"highlighting":[139],"involvement":[141],"microbiota–host":[143],"interactions":[145],"shaping":[147],"these":[148,155,193],"changes.":[150],"We":[151],"further":[152],"explore":[153],"metabolites,":[156],"through":[157,277],"specific":[159],"FXR/TGR5,":[162],"FFAR2/3,":[163],"mGluRs,":[164],"LPAR),":[165],"transduce":[166],"signals":[168],"into":[169],"changes":[170,287],"neuroinflammation":[172],"neuronal":[174,201],"excitability.":[175],"Crucially,":[176],"modifications":[178],"(DNA":[179],"methylation,":[180],"non-coding":[181],"RNAs,":[182],"histone":[184],"modifications)":[185],"may":[186,271],"long-term":[190],"alterations":[194],"by":[195],"transcriptional":[197],"programs":[198],"plasticity":[202],"inflammation,":[204],"providing":[205,260],"potential":[207],"molecular":[208],"basis":[209,263],"for":[210,264],"concept":[212],"pain":[214],"\\"memory\\"":[215],"after":[216],"chemotherapy":[217],"cessation.":[218],"Based":[219],"this":[221],"analysis,":[222],"we":[223],"propose":[224],"\\"metabolites-":[226],"metabolite-linked":[227,291],"receptors-":[228,292],"regulation\\"":[230],"framework,":[231],"aiming":[232],"connect":[234],"disturbances":[237],"local":[239],"neuropathic":[240],"changes,":[241],"acute":[243],"injury":[244],"chronic":[246],"pain.":[247],"framework":[249,294],"integrates":[250],"remodeling,":[253],"metabolite":[254],"sensing":[255],"pathways,":[256],"mechanisms,":[259],"conceptual":[262],"maintenance.":[269],"It":[270],"also":[272],"offer":[273],"novel":[274],"therapeutic":[275],"opportunities":[276],"intervention,":[279],"receptor":[280],"targeting,":[281],"modulation.":[284],"Chemotherapy":[285],"induces":[286],"\\"metabolism-":[290],"epigenetics\\"":[293],"potentially":[296],"influences":[297],"CIPN.":[301],"CIPN,":[302],"Chemotherapy-Induced":[303],"Peripheral":[304],"Neuropathy;":[305],"BA,":[306],"Bile":[307],"Acid;":[308,311],"DCA,":[309],"Deoxycholic":[310],"ω-MCA,":[312],"ω-Muricholic":[313],"acid;":[314,321],"Glu,":[315],"Glutamate;":[316],"BCAA,":[317],"branched":[318],"chain":[319],"Trp,":[322],"Tryptophan;":[323],"Kyn,":[324],"Kynurenine;":[325],"Cer,":[326,327],"Ceramide;":[328],"Sph,":[329],"Sphingosine;":[330],"S1P,":[331],"Sphingosine-1-phosphate.":[332]}

Authors

Institutions

Publication Details

Journal
Cell Biology and Toxicology
Published
2026-09-15
DOI
https://doi.org/10.1007/s10565-026-10275-z
Primary Topic
Cancer Treatment and Pharmacology
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Chemotherapy-induced peripheral neuropathy: emerging roles of metabolic reprogramming, signal sensing, and epigenetic plasticity

Songsong Pan, Qianhao Hou, Lijun Liao, Zihao Zheng et al.
Cell Biology and Toxicology
Cancer Treatment and Pharmacology
article

Chemotherapy-induced peripheral neuropathy: emerging roles of metabolic reprogramming, signal sensing, and epigenetic plasticity

Songsong Pan, Qianhao Hou, Lijun Liao, Zihao Zheng, Lihui Liu
article en

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and persistent adverse effects of cancer treatment, particularly associated with platinum-based compounds (e.g., oxaliplatin and cisplatin), taxanes (e.g., paclitaxel and docetaxel), vinca alkaloids, and proteasome inhibitors. Traditional studies have linked its development to microtubule damage, mitochondrial dysfunction, and ion channel abnormalities. However, with the advancement of metabolomics in recent years, the contribution of systemic metabolic remodeling and gut microbiota-derived metabolites to CIPN pathogenesis has become increasingly recognized. The role of metabolites and their corresponding receptors in regulating neuropathy have become increasingly recognized, including their impact on epigenetic modifications. To date, a comprehensive understanding of how various metabolites contribute to the onset and persistence of CIPN is still lacking. This review synthesizes current evidence on chemotherapy-induced metabolic reprogramming, focusing on bile acids, short-chain fatty acids, amino acids, and lipids, while highlighting the involvement of microbiota–host metabolic interactions in shaping these metabolic changes. We further explore how these metabolites, through their specific receptors (e.g., FXR/TGR5, FFAR2/3, mGluRs, LPAR), transduce metabolic signals into changes in neuroinflammation and neuronal excitability. Crucially, epigenetic modifications (DNA methylation, non-coding RNAs, and histone modifications) may contribute to the long-term persistence of these alterations by regulating transcriptional programs associated with neuronal plasticity and inflammation, providing a potential molecular basis for the concept of pain "memory" after chemotherapy cessation. Based on this analysis, we propose a "metabolites- metabolite-linked receptors- epigenetic regulation" framework, aiming to connect systemic metabolic disturbances with local neuropathic changes, and acute injury with chronic pain. This framework integrates chemotherapy-induced metabolic remodeling, metabolite sensing pathways, and epigenetic mechanisms, providing a conceptual basis for understanding CIPN development and maintenance. It may also offer novel therapeutic opportunities through metabolic intervention, receptor targeting, and epigenetic modulation. Chemotherapy induces changes in the "metabolism- metabolite-linked receptors- epigenetics" framework and potentially influences the development of CIPN. CIPN, Chemotherapy-Induced Peripheral Neuropathy; BA, Bile Acid; DCA, Deoxycholic Acid; ω-MCA, ω-Muricholic acid; Glu, Glutamate; BCAA, branched chain amino acid; Trp, Tryptophan; Kyn, Kynurenine; Cer, Cer, Ceramide; Sph, Sphingosine; S1P, Sphingosine-1-phosphate.

Cell Biology and Toxicology
Tongji University (CN), Shanghai East Hospital (CN)
Good health and well-being
Openalex Percentile: Top 14%
Cancer Treatment and Pharmacology
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.