{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T16:57:47Z","timestamp":1781456267279,"version":"3.54.1"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.phrs.2026.108248","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:38:13Z","timestamp":1778758693000},"page":"108248","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["ACSS2 drives Lenvatinib resistance in hepatocellular carcinoma through palmitoylation"],"prefix":"10.1016","volume":"229","author":[{"given":"Hao","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Zhe","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Tian","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Zhe","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Jie","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SamI","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Song","family":"CHEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Han","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun-Xiu","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.phrs.2026.108248_bib1","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.cgh.2023.01.039","article-title":"Breakthroughs in hepatocellular carcinoma therapies","volume":"21","author":"Singal","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"10126","key":"10.1016\/j.phrs.2026.108248_bib2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"issue":"15","key":"10.1016\/j.phrs.2026.108248_bib3","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1200\/JCO.23.02745","article-title":"Systemic therapy for advanced hepatocellular carcinoma: ASCO Guideline Update","volume":"42","author":"Gordan","year":"2024","journal-title":"J. Clin. Oncol."},{"issue":"4","key":"10.1016\/j.phrs.2026.108248_bib4","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/HEP.0000000000000237","article-title":"Mechanisms of drug resistance in HCC","volume":"79","author":"Ladd","year":"2024","journal-title":"Hepatology"},{"issue":"6487","key":"10.1016\/j.phrs.2026.108248_bib5","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"issue":"8","key":"10.1016\/j.phrs.2026.108248_bib6","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1172\/JCI127201","article-title":"Adipocyte and lipid metabolism in cancer drug resistance","volume":"129","author":"Cao","year":"2019","journal-title":"J. Clin. Invest"},{"issue":"1","key":"10.1016\/j.phrs.2026.108248_bib7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s13046-019-1214-z","article-title":"The roles of glucose metabolic reprogramming in chemo- and radio-resistance","volume":"38","author":"Lin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res"},{"issue":"3","key":"10.1016\/j.phrs.2026.108248_bib8","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.trecan.2020.10.004","article-title":"Fat and Furious: Lipid Metabolism in Antitumoral Therapy Response and Resistance","volume":"7","author":"Bacci","year":"2021","journal-title":"Trends Cancer"},{"issue":"46","key":"10.1016\/j.phrs.2026.108248_bib9","article-title":"Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC","volume":"11","author":"Lu","year":"2024","journal-title":"Adv. Sci. (Weinh. )"},{"key":"10.1016\/j.phrs.2026.108248_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2023.100976","article-title":"Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression","volume":"69","author":"Wang","year":"2023","journal-title":"Drug Resist Updat"},{"issue":"17","key":"10.1016\/j.phrs.2026.108248_bib11","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1158\/0008-5472.CAN-21-2934","article-title":"Caspase-3-Induced Activation of SREBP2 drives drug resistance via promotion of cholesterol biosynthesis in hepatocellular carcinoma","volume":"82","author":"Mok","year":"2022","journal-title":"Cancer Res"},{"issue":"5","key":"10.1016\/j.phrs.2026.108248_bib12","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1158\/0008-5472.CAN-20-1847","article-title":"Targeting ACSS2 with a transition-state mimetic inhibits triple-negative breast cancer growth","volume":"81","author":"Miller","year":"2021","journal-title":"Cancer Res"},{"issue":"1","key":"10.1016\/j.phrs.2026.108248_bib13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13024-023-00625-4","article-title":"ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer's disease","volume":"18","author":"Lin","year":"2023","journal-title":"Mol. Neurodegener."},{"issue":"4","key":"10.1016\/j.phrs.2026.108248_bib14","doi-asserted-by":"crossref","DOI":"10.1172\/JCI172963","article-title":"ACSS2 gene variants determine kidney disease risk by controlling de novo lipogenesis in kidney tubules","volume":"134","author":"Mukhi","year":"2023","journal-title":"J. Clin. Invest"},{"issue":"1","key":"10.1016\/j.phrs.2026.108248_bib15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ccell.2014.12.002","article-title":"Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress","volume":"27","author":"Schug","year":"2015","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phrs.2026.108248_bib16","article-title":"Nutrient-driven histone code determines exhausted CD8(+) T cell fates","author":"Ma","year":"2024","journal-title":"Science"},{"issue":"3","key":"10.1016\/j.phrs.2026.108248_bib17","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cmet.2020.07.004","article-title":"Memory CD8(+) T cells balance pro- and anti-inflammatory activity by reprogramming cellular acetate handling at sites of infection","volume":"32","author":"Balmer","year":"2020","journal-title":"Cell Metab."},{"issue":"9","key":"10.1016\/j.phrs.2026.108248_bib18","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20231820","article-title":"ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses","volume":"221","author":"Kaymak","year":"2024","journal-title":"J. Exp. Med"},{"issue":"20","key":"10.1016\/j.phrs.2026.108248_bib19","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1158\/0008-5472.CAN-21-4140","article-title":"Inhibition of EGFR overcomes acquired lenvatinib resistance driven by STAT3-ABCB1 signaling in hepatocellular carcinoma","volume":"82","author":"Hu","year":"2022","journal-title":"Cancer Res"},{"issue":"7869","key":"10.1016\/j.phrs.2026.108248_bib20","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41586-021-03741-7","article-title":"EGFR activation limits the response of liver cancer to lenvatinib","volume":"595","author":"Jin","year":"2021","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.phrs.2026.108248_bib21","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1002\/hep.32177","article-title":"Integration of glucose and cardiolipin anabolism confers radiation resistance of HCC","volume":"75","author":"Fang","year":"2022","journal-title":"Hepatology"},{"issue":"23","key":"10.1016\/j.phrs.2026.108248_bib22","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1161\/CIRCULATIONAHA.120.051937","article-title":"Suppression of myocardial hypoxia-inducible factor-1\u03b1 compromises metabolic adaptation and impairs cardiac function in patients with cyanotic congenital heart disease during puberty","volume":"143","author":"Liu","year":"2021","journal-title":"Circulation"},{"issue":"19","key":"10.1016\/j.phrs.2026.108248_bib23","doi-asserted-by":"crossref","first-page":"6529","DOI":"10.1128\/AEM.01178-10","article-title":"Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655","volume":"76","author":"Portnoy","year":"2010","journal-title":"Appl. Environ. Microbiol"},{"issue":"101","key":"10.1016\/j.phrs.2026.108248_bib24","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adp7302","article-title":"Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity","volume":"9","author":"Zhang","year":"2024","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.phrs.2026.108248_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2023.216122","article-title":"METTL3-m(6)A-EGFR-axis drives lenvatinib resistance in hepatocellular carcinoma","volume":"559","author":"Wang","year":"2023","journal-title":"Cancer Lett."},{"issue":"5","key":"10.1016\/j.phrs.2026.108248_bib26","doi-asserted-by":"crossref","first-page":"684","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"},{"issue":"2","key":"10.1016\/j.phrs.2026.108248_bib27","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/15548627.2022.2062112","article-title":"Acetylation in the regulation of autophagy","volume":"19","author":"Xu","year":"2023","journal-title":"Autophagy"},{"issue":"7","key":"10.1016\/j.phrs.2026.108248_bib28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.metabol.2014.04.003","article-title":"De novo lipogenesis in health and disease","volume":"63","author":"Ameer","year":"2014","journal-title":"Metabolism"},{"issue":"7","key":"10.1016\/j.phrs.2026.108248_bib29","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.cell.2014.11.020","article-title":"Acetate dependence of tumors","volume":"159","author":"Comerford","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2026.108248_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2019.100670","article-title":"Phospholipids and cholesterol: Inducers of cancer multidrug resistance and therapeutic targets","volume":"49","author":"Kopecka","year":"2020","journal-title":"Drug Resist Updat"},{"issue":"11","key":"10.1016\/j.phrs.2026.108248_bib31","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.trecan.2024.08.005","article-title":"Metabolism and epigenetics: drivers of tumor cell plasticity and treatment outcomes","volume":"10","author":"Gantner","year":"2024","journal-title":"Trends Cancer"},{"issue":"4","key":"10.1016\/j.phrs.2026.108248_bib32","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.celrep.2016.09.069","article-title":"ATP-Citrate lyase controls a glucose-to-acetate metabolic switch","volume":"17","author":"Zhao","year":"2016","journal-title":"Cell Rep."},{"issue":"3","key":"10.1016\/j.phrs.2026.108248_bib33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.bbalip.2018.06.005","article-title":"Glucose-derived acetate and ACSS2 as key players in cisplatin resistance in bladder cancer","volume":"1864","author":"Wen","year":"2019","journal-title":"Biochim Biophys. Acta Mol. Cell Biol. Lipids"},{"issue":"8","key":"10.1016\/j.phrs.2026.108248_bib34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0962-8924(99)01608-6","article-title":"Getting across the nuclear pore complex","volume":"9","author":"Talcott","year":"1999","journal-title":"Trends Cell Biol."},{"issue":"10","key":"10.1016\/j.phrs.2026.108248_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/nu10101383","article-title":"Regulation and metabolic significance of de novo lipogenesis in adipose tissues","volume":"10","author":"Song","year":"2018","journal-title":"Nutrients"},{"issue":"14","key":"10.1016\/j.phrs.2026.108248_bib36","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.7150\/ijbs.45640","article-title":"S-Palmitoylation as a functional regulator of proteins associated with cisplatin resistance in bladder cancer","volume":"16","author":"Shahid","year":"2020","journal-title":"Int J. Biol. Sci."},{"issue":"1","key":"10.1016\/j.phrs.2026.108248_bib37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s11658-024-00625-2","article-title":"Palmitoylation of synaptic proteins: roles in functional regulation and pathogenesis of neurodegenerative diseases","volume":"29","author":"Peng","year":"2024","journal-title":"Cell Mol. Biol. Lett."},{"issue":"3","key":"10.1016\/j.phrs.2026.108248_bib38","article-title":"Protein palmitoylation: biological functions, disease, and therapeutic targets","volume":"6","author":"Qian","year":"2025","journal-title":"MedComm (2020)"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826001635?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826001635?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T16:20:45Z","timestamp":1781454045000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661826001635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":38,"alternative-id":["S1043661826001635"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108248","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"ACSS2 drives Lenvatinib resistance in hepatocellular carcinoma through palmitoylation","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108248","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108248"}}