{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:03:40Z","timestamp":1791198220022,"version":"4.1.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA268383, P30CA023074"],"award-info":[{"award-number":["R01CA268383, P30CA023074"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Epigenetic therapies can reverse malignant transcriptional programs, but their activity is often constrained by adaptive stress responses that allow cancer cells to survive and recover. Autophagy is a central component of this adaptation. By sustaining metabolic homeostasis, mitochondrial fitness, proteostasis, and lysosomal recycling, autophagy can buffer the cellular injury produced by inhibitors of DNA methyltransferases, histone deacetylases, and bromodomain proteins. These observations provide a strong rationale for combining epigenetic therapies with autophagy inhibition. However, the field has too often equated autophagosome accumulation with increased autophagic flux and treatment-induced autophagy with a functional dependency. Moreover, the lysosomotropic agents used in early clinical studies incompletely inhibit autophagy and exert broader effects on lysosomal biology. Consequently, compelling preclinical activity has not translated into consistent clinical benefit. Here, we critically evaluate the mechanisms through which epigenetic therapies engage autophagy, distinguish correlative markers from causal evidence of resistance, and assess the preclinical and clinical data supporting combination strategies. We also define the major barriers to translation, including inadequate pharmacodynamic assays, a lack of predictive biomarkers, context-dependent effects on tumor and immune cells, and the limited potency and selectivity of current autophagy inhibitors. Defining when, where, and how autophagy becomes a targetable dependency will be essential to translate this compelling biology into an effective precision treatment.<\/jats:p>","DOI":"10.3389\/fonc.2026.1985943","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:43:35Z","timestamp":1791197015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Autophagy as an adaptive resistance mechanism to epigenetic therapy in cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Natalie L.","family":"Hakim","sequence":"first","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Thomas","family":"Gialluisi","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruthi","family":"Sureshkumar","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison E.","family":"Gamble","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Espitia","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Southern California Keck School of Medicine","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Carew","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffan T.","family":"Nawrocki","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Department of Medicine and University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The emerging hallmarks of cancer metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.53","article-title":"Targeting autophagy in cancer","volume":"17","author":"Levy","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/path.2697","article-title":"Autophagy: cellular and molecular mechanisms","volume":"221","author":"Glick","year":"2010","journal-title":"J Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat Cell Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2757","article-title":"ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase","volume":"15","author":"Russell","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nrm3716","article-title":"The return of the nucleus: transcriptional and epigenetic control of autophagy","volume":"15","author":"Fullgrabe","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.cell.2012.06.013","article-title":"Cancer epigenetics: from mechanism to therapy","volume":"150","author":"Dawson","year":"2012","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41420-024-01803-z","article-title":"Cancer epigenetics: from laboratory studies and clinical trials to precision medicine","volume":"10","author":"Yu","year":"2024","journal-title":"Cell Death Discov"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrg816","article-title":"The fundamental role of epigenetic events in cancer","volume":"3","author":"Jones","year":"2002","journal-title":"Nat Rev Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13072-017-0130-8","article-title":"DNA methylation and DNA methyltransferases","volume":"10","author":"Edwards","year":"2017","journal-title":"Epigenet Chromatin"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/jci69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J Clin Invest"},{"key":"B13","doi-asserted-by":"publisher","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of MicroRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct Target Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121656","article-title":"Epigenetic control of autophagy in cancer cells: a key process for cancer-related phenotypes","volume":"8","author":"Peixoto","year":"2019","journal-title":"Cells"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1034410","article-title":"Transcriptional and epigenetic regulation of autophagy in aging","volume":"11","author":"Lapierre","year":"2015","journal-title":"Autophagy"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1816664","article-title":"The DNA methyltransferase DNMT3A contributes to autophagy long-term memory","volume":"17","author":"Gonzalez-Rodriguez","year":"2021","journal-title":"Autophagy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cell.2013.03.004","article-title":"Influence of metabolism on epigenetics and disease","volume":"153","author":"Kaelin","year":"2013","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/jci73941","article-title":"The role for autophagy in cancer","volume":"125","author":"White","year":"2015","journal-title":"J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008821","article-title":"Autophagy and cancer","volume":"4","author":"Mah","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002666","article-title":"Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis","volume":"5","author":"Dykstra","year":"2021","journal-title":"Blood Adv"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-19-0292","article-title":"Targeting autophagy in cancer: recent advances and future directions","volume":"9","author":"Amaravadi","year":"2019","journal-title":"Cancer Discov"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-16-0722","article-title":"The challenge of developing autophagy inhibition as a therapeutic strategy","volume":"76","author":"Gewirtz","year":"2016","journal-title":"Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1280222","article-title":"Drain the lysosome: development of the novel orally available autophagy inhibitor ROC-325","volume":"13","author":"Carew","year":"2017","journal-title":"Autophagy"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29231","article-title":"Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors","volume":"10","author":"Mahalingam","year":"2014","journal-title":"Autophagy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s40880-019-0418-0","article-title":"Moving beyond hydroxychloroquine: the novel lysosomal autophagy inhibitor ROC-325 shows significant potential in preclinical studies","volume":"39","author":"Jones","year":"2019","journal-title":"Cancer Commun (Lond)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1988357","article-title":"GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions","volume":"18","author":"Brun","year":"2022","journal-title":"Autophagy"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2024.2403152","article-title":"Divergent effects of acute and chronic PPT1 inhibition in melanoma","volume":"21","author":"Crissey","year":"2024","journal-title":"Autophagy"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7554\/elife.96992.3","article-title":"Inhibition of ULK1\/2 and KRAS(G12C) controls tumor growth in preclinical models of lung cancer","volume":"13","author":"Ghazi","year":"2024","journal-title":"Elife"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/cancers18111746","article-title":"Divergent role of ULK1 to balance mitochondrial homeostasis and bioenergetics in ovarian cancer spheroids","volume":"18","author":"Webb","year":"2026","journal-title":"Cancers (Basel)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29119","article-title":"Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma","volume":"10","author":"Rangwala","year":"2014","journal-title":"Autophagy"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4161\/auto.28984","article-title":"A phase I\/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme","volume":"10","author":"Rosenfeld","year":"2014","journal-title":"Autophagy"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29264","article-title":"Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed\/refractory myeloma","volume":"10","author":"Vogl","year":"2014","journal-title":"Autophagy"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217496","article-title":"REDD1 is a determinant of the sensitivity of renal cell carcinoma cells to autophagy inhibition that can be therapeutically exploited by targeting PIM activity","volume":"613","author":"Carew","year":"2025","journal-title":"Cancer Lett"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.295","article-title":"Complete mutational spectrum of the autophagy interactome: a novel class of tumor suppressor genes in myeloid neoplasms","volume":"31","author":"Visconte","year":"2017","journal-title":"Leukemia"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019505","article-title":"Epigenetic determinants of cancer","volume":"8","author":"Baylin","year":"2016","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.cd-21-1059","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2008.08.006","article-title":"DNA methylation in development and human disease","volume":"647","author":"Gopalakrishnan","year":"2008","journal-title":"Mutat Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1038\/ncponc0354","article-title":"DNA methylation and gene silencing in cancer","volume":"2","author":"Baylin","year":"2005","journal-title":"Nat Clin Pract Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.292","article-title":"Post-translational modifications of histones: mechanisms, biological functions, and therapeutic targets","volume":"4","author":"Liu","year":"2023","journal-title":"MedComm (2020)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1997","article-title":"MicroRNA signatures in human cancers","volume":"6","author":"Calin","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40364-019-0174-y","article-title":"Epigenetic heterogeneity in cancer","volume":"7","author":"Guo","year":"2019","journal-title":"biomark Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1172\/jci178540","article-title":"Epigenetic regulation of tumor immunity","volume":"134","author":"Pang","year":"2024","journal-title":"J Clin Invest"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00302-4","article-title":"Non-genetic mechanisms of therapeutic resistance in cancer","volume":"20","author":"Marine","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal2380","article-title":"Epigenetic plasticity and the hallmarks of cancer","volume":"357","author":"Flavahan","year":"2017","journal-title":"Science"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.93","article-title":"Targeting the cancer epigenome for therapy","volume":"17","author":"Jones","year":"2016","journal-title":"Nat Rev Genet"},{"key":"B47","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cell.2010.02.027","article-title":"A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations","volume":"141","author":"Sharma","year":"2010","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(09)70003-8","article-title":"Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study","volume":"10","author":"Fenaux","year":"2009","journal-title":"Lancet Oncol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2006.10.2434","article-title":"Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma","volume":"25","author":"Olsen","year":"2007","journal-title":"J Clin Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(14)70440-1","article-title":"Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial","volume":"15","author":"San-Miguel","year":"2014","journal-title":"Lancet Oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050260","article-title":"Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance","volume":"110","author":"Carew","year":"2007","journal-title":"Blood"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0529-2","article-title":"The novel autophagy inhibitor ROC-325 augments the antileukemic activity of azacitidine","volume":"33","author":"Nawrocki","year":"2019","journal-title":"Leukemia"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1214780","article-title":"Epigenetic and transcriptional regulation of autophagy","volume":"12","author":"Shin","year":"2016","journal-title":"Autophagy"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-02006-w","article-title":"Histone demethylases in autophagy and inflammation","volume":"23","author":"Ma","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B55","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41392-022-01300-8","article-title":"Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets","volume":"8","author":"Shu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4161\/auto.9064","article-title":"Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells","volume":"5","author":"Zhu","year":"2009","journal-title":"Autophagy"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204592","article-title":"TFEB links autophagy to lysosomal biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"B58","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/cells4020135","article-title":"HDAC family members intertwined in the regulation of autophagy: A druggable vulnerability in aggressive tumor entities","volume":"4","author":"Koeneke","year":"2015","journal-title":"Cells"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nature15548","article-title":"Autophagy mediates degradation of nuclear lamina","volume":"527","author":"Dou","year":"2015","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1101\/gad.223834.113","article-title":"Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape","volume":"27","author":"Shah","year":"2013","journal-title":"Genes Dev"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.04.026","article-title":"Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy","volume":"66","author":"Li","year":"2017","journal-title":"Mol Cell"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712145105","article-title":"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy","volume":"105","author":"Lee","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"B64","doi-asserted-by":"publisher","first-page":"7215","DOI":"10.1038\/ncomms8215","article-title":"Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth","volume":"6","author":"Sun","year":"2015","journal-title":"Nat Commun"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00832.x","article-title":"Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation","volume":"14","author":"Carew","year":"2010","journal-title":"J Cell Mol Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02250-6","article-title":"Autophagy degrades immunogenic endogenous retroelements induced by 5-azacytidine in acute myeloid leukemia","volume":"38","author":"Noronha","year":"2024","journal-title":"Leukemia"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-11-0979","article-title":"Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts superior efficacy against triple-negative human breast cancer cells","volume":"11","author":"Rao","year":"2012","journal-title":"Mol Cancer Ther"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2021.04.003","article-title":"Synergistic effect of Chloroquine and Panobinostat in ovarian cancer through induction of DNA damage and inhibition of DNA repair","volume":"23","author":"Ovejero-Sanchez","year":"2021","journal-title":"Neoplasia"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-16-1903","article-title":"AMPK-ULK1-mediated autophagy confers resistance to BET inhibitor JQ1 in acute myeloid leukemia stem cells","volume":"23","author":"Jang","year":"2017","journal-title":"Clin Cancer Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1985943\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:43:37Z","timestamp":1791197017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1985943\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":69,"alternative-id":["10.3389\/fonc.2026.1985943"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1985943","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1985943"}}