[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-371069-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-371069-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","targeting-lactylation-offers-therapy-to-reverse-cell-death-resistance","Targeting Lactylation Offers Therapy to Reverse Cell Death Resistance","","Lactylation, a lactate-derived post-translational modification, functions as a master metabolic regulator of resistance to regulated cell death (RCD) across cancer, inflammatory disorders, and degenerative diseases. Through lactyltransferases and delactylases, lactylation dynamically modifies histones and non-histone proteins, coordinating molecular pathways that suppress ferroptosis, cuproptosis, and apoptosis. This review synthesizes lactylation’s mechanisms, evaluates its disease implications, and outlines emerging therapies targeting lactylation regulators or combining lactate modulation with RCD inducers to overcome refractory cancer conditions.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/targeting-lactylation-offers-therapy-to-reverse-cell-death-resistance/371069/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/targeting-lactylation-offers-therapy-to-reverse-cell-death-resistance/371069.png","ImageObject",300,407,{"name":42,"@type":43},"dhado","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",18,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is lactylation and why is it important in disease?","Question",{"text":63,"@type":64},"Lactylation is a lactate-derived post-translational modification that acts as a key metabolic regulator. It emerges as an important mechanism connecting metabolism to gene and protein regulation during disease progression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does lactylation affect regulated cell death pathways?",{"text":68,"@type":64},"Lactylation suppresses multiple RCD modalities by coordinating convergent molecular pathways. It inhibits ferroptosis, cuproptosis, and apoptosis through regulation of the execution machinery and gene/protein programs.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic strategies does the review discuss for targeting lactylation?",{"text":72,"@type":64},"The review discusses disrupting lactylation-mediated cell death evasion by targeting lactylation regulators (writers/erasers). 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By dynamically modifying histones and non-histone proteins via lactyltransferases and delactylases, lactylation orchestrates convergent molecular pathways that suppress ferroptosis, cuproptosis, and apoptosis. This review synthesizes current understanding of lactylation asa central regulator of RCD resistance in diseases, especially in cancers. We dissect the molecular machinery through which lactylation subverts ferroptosis, cuproptosis, and apoptosis; evaluate its pathophysiological implications in diverse pathologies; and discuss emerging therapeutic strategies to disrupt lactylation-mediated cell death evasion. This metabolic-epigenetic crosstalk establishes a robust shield against RCD in disease microenvironments, promoting therapeutic resistance and pathological resilience. Targeting lactylation regulators (writers/erasers) or combining lactate modulation with RCD inducers represents a promising strategy to overcome treatment-refractory conditions in cancers.\u003Cbr>Keywords: lactylation, regulated cell death, ferroptosis, cuproptosis, apoptosis |\n| --- |\n| Introduction\u003Cbr>Metabolic reprogramming is a fundamental hallmark of diverse pathological states, driving the accumulation of metabolites like lactate that serve as precursors for novel post-translational modifications. Among these, lysine lactylation (Kla)—a lactate-derived epigenetic mark initially identified in macrophages—has emerged as a critical regulator of gene expression beyond immunomodulation. Elevated lactate levels, characteristic of inflammatory microenvironments, ischemic tissues, and metabolic disorders, provide the substrate for enzymatic lactylation catalyzed by acyltransferases such as p300 and KAT7 . This modification directly links cellular metabolism to epigenetic and non-epigenetic reprogramming, enabling contextdependent adaptations in disease progression. Crucially, lactylation’s influence extends to the regulation of fundamental cell death pathways, where it orchestrates resistance mechanisms that compromise tissue homeostasis and promote pathological resilience across cancer, neurodeg","cbCaiuOOWQqFypQs","https://ap.wps.com/l/cbCaiuOOWQqFypQs","pdf",10053627,24,"English","# Abstract\n# Introduction","[{\"question\":\"What is lactylation and why is it important in disease?\",\"answer\":\"Lactylation is a lactate-derived post-translational modification that acts as a key metabolic regulator. It emerges as an important mechanism connecting metabolism to gene and protein regulation during disease progression.\"},{\"question\":\"How does lactylation affect regulated cell death pathways?\",\"answer\":\"Lactylation suppresses multiple RCD modalities by coordinating convergent molecular pathways. It inhibits ferroptosis, cuproptosis, and apoptosis through regulation of the execution machinery and gene/protein programs.\"},{\"question\":\"What therapeutic strategies does the review discuss for targeting lactylation?\",\"answer\":\"The review discusses disrupting lactylation-mediated cell death evasion by targeting lactylation regulators (writers/erasers). It also highlights combining lactate modulation with RCD inducers to improve treatment outcomes, especially in cancers.\"}]","Targeting Lactylation Offers Therapy to Reverse Cell Death Resistance | PDF",1790191174]