{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:32:47Z","timestamp":1792171967339,"version":"4.4.0"},"reference-count":232,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Isocitrate dehydrogenase (IDH) mutations represent pivotal oncogenic drivers across multiple malignancies. Mutant IDH enzymes acquire neomorphic activity that produces the oncometabolite\n                    <jats:sc>D<\/jats:sc>\n                    \u20102\u2010hydroxyglutarate (D\u20102HG), which competitively inhibits \u03b1\u2010ketoglutarate\u2010dependent dioxygenases and promotes epigenetic reprogramming, differentiation arrest, and malignant transformation. Beyond tumor cell\u2013intrinsic effects, D\u20102HG profoundly remodels the tumor immune microenvironment by directly suppressing T\u2010cell proliferation and effector functions, silencing natural killer (NK) cell\u2010activating ligands, and impairing dendritic cell maturation. In this review, we delineate the mechanistic basis of mutant IDH in oncogenesis and evaluate the development of selective allosteric inhibitors validated through rigorous preclinical models demonstrating potent D\u20102HG suppression. Clinical translation has yielded multiple FDA\u2010approved IDH inhibitors demonstrating significant therapeutic efficacy across diverse IDH\u2010mutant malignancies. Notably, dual inhibitors have extended progression\u2010free survival in gliomas, whereas triple\u2010combination regimens have achieved substantial complete remission rates in acute myeloid leukemia. However, therapeutic resistance has emerged through second\u2010site mutations, clonal evolution, and metabolic reprogramming. We also discuss rational combinatorial strategies integrating IDH inhibitors with hypomethylating agents (HMAs), targeted therapies, and immunomodulatory approaches, alongside emerging technologies such as single\u2010cell profiling and spatial transcriptomics. By addressing both achievements and challenges, this review underscores the translational relevance of IDH\u2010targeted therapy and its potential to reshape precision oncology through refined patient stratification and enhanced therapeutic efficacy.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70732","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:41:38Z","timestamp":1776667298000},"source":"Crossref","is-referenced-by-count":3,"title":["Isocitrate Dehydrogenase Mutations in Cancer: From Bench to Bedside Applications"],"prefix":"10.1002","volume":"7","author":[{"given":"Yuhan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of General Surgery The Second Hospital of Dalian Medical University  Dalian China"},{"name":"Institute (College) of Integrative Medicine Dalian Medical University  Dalian China"},{"name":"Laboratory of Integrative Medicine The First Affiliated Hospital of Dalian Medical University  Dalian 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Chand","family":"Dakal","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Mohanlal Sukhadia University  Udaipur Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-2301","authenticated-orcid":false,"given":"Caiming","family":"Xu","sequence":"additional","affiliation":[{"name":"Beckman Research Institute of City of Hope Biomedical Research Center  Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Hospital of Dalian Medical University  Dalian China"},{"name":"Institute (College) of Integrative Medicine Dalian Medical University 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