{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:35:56Z","timestamp":1791516956350,"version":"4.3.4"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008665","name":"Universit\u00e9 du Luxembourg","doi-asserted-by":"publisher","award":["Do373\/13 \\u2013 1"],"award-info":[{"award-number":["Do373\/13 \\u2013 1"]}],"id":[{"id":"10.13039\/100008665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031L0037"],"award-info":[{"award-number":["031L0037"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["PTJ-FKZ: 031 L0043"],"award-info":[{"award-number":["PTJ-FKZ: 031 L0043"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Me4532\/1 \\u2013 1"],"award-info":[{"award-number":["Me4532\/1 \\u2013 1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010007","name":"Chinesisch-Deutsche Zentrum f\u00fcr Wissenschaftsf\u00f6rderung","doi-asserted-by":"publisher","award":["GZ126"],"award-info":[{"award-number":["GZ126"]}],"id":[{"id":"10.13039\/501100010007","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010441","name":"Medizinischen Fakult\u00e4t Heidelberg, Universit\u00e4t Heidelberg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010441","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE26370"],"award-info":[{"award-number":["GSE26370"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE57951"],"award-info":[{"award-number":["GSE57951"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE14520"],"award-info":[{"award-number":["GSE14520"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE25097"],"award-info":[{"award-number":["GSE25097"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE14323"],"award-info":[{"award-number":["GSE14323"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE123062"],"award-info":[{"award-number":["GSE123062"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["GSE39791"],"award-info":[{"award-number":["GSE39791"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["MDA-MB-231"],"award-info":[{"award-number":["MDA-MB-231"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EBioMedicine"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1016\/j.ebiom.2020.102699","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T11:58:20Z","timestamp":1587470300000},"page":"102699","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"special_numbering":"C","title":["Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance"],"prefix":"10.1016","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-2045","authenticated-orcid":false,"given":"Zeribe Chike","family":"Nwosu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Pioro\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Battello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas David","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bedair","family":"Dewidar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Blagojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darko","family":"Castven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verodia","family":"Charlestin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-2621","authenticated-orcid":false,"given":"Pavlo","family":"Holenya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lochead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"De La Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Gretz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sajjakulnukit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew H.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens U.","family":"Marquardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Pasca","family":"di Magliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costas A.","family":"Lyssiotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sleeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"W\u00f6lfl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias Philip","family":"Ebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Dooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9972","key":"10.1016\/j.ebiom.2020.102699_bib0001","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/S0140-6736(14)62038-9","article-title":"Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)","volume":"385","author":"Allemani","year":"2015","journal-title":"Lancet"},{"issue":"4","key":"10.1016\/j.ebiom.2020.102699_bib0002","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaoncol.2015.0735","article-title":"The global burden of cancer 2013","volume":"1","author":"Fitzmaurice","year":"2015","journal-title":"JAMA Oncol"},{"issue":"10","key":"10.1016\/j.ebiom.2020.102699_bib0003","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrc4000","article-title":"MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road","volume":"15","author":"Caunt","year":"2015","journal-title":"Nat Rev Cancer"},{"issue":"11","key":"10.1016\/j.ebiom.2020.102699_bib0004","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/nm.3388","article-title":"The quest to overcome resistance to EGFR-targeted therapies in cancer","volume":"19","author":"Chong","year":"2013","journal-title":"Nat Med"},{"issue":"10","key":"10.1016\/j.ebiom.2020.102699_bib0005","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer drug resistance: an evolving paradigm","volume":"13","author":"Holohan","year":"2013","journal-title":"Nat Rev Cancer"},{"issue":"10064","key":"10.1016\/j.ebiom.2020.102699_bib0006","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.ebiom.2020.102699_bib0007","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1158\/1078-0432.CCR-13-0547","article-title":"Hepatocellular carcinoma: reasons for phase iii failure and novel perspectives on trial design","volume":"20","author":"Llovet","year":"2014","journal-title":"Clin Cancer Res"},{"issue":"6","key":"10.1016\/j.ebiom.2020.102699_bib0008","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1200\/JCO.2013.53.7746","article-title":"SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma","volume":"33","author":"Zhu","year":"2015","journal-title":"J Clin Oncol"},{"issue":"1","key":"10.1016\/j.ebiom.2020.102699_bib0009","doi-asserted-by":"crossref","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"},{"issue":"4","key":"10.1016\/j.ebiom.2020.102699_bib0010","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","article-title":"Understanding the intersections between metabolism and cancer biology","volume":"168","author":"Vander Heiden","year":"2017","journal-title":"Cell"},{"issue":"21","key":"10.1016\/j.ebiom.2020.102699_bib0011","doi-asserted-by":"crossref","first-page":"6374","DOI":"10.1158\/0008-5472.CAN-16-1559","article-title":"Integrative genomic analysis identifies the core transcriptional hallmarks of human hepatocellular carcinoma","volume":"76","author":"Allain","year":"2016","journal-title":"Cancer Res"},{"issue":"7","key":"10.1016\/j.ebiom.2020.102699_bib0012","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and integrative genomic characterization of hepatocellular carcinoma","volume":"169","year":"2017","journal-title":"Cell"},{"issue":"7","key":"10.1016\/j.ebiom.2020.102699_bib0013","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/bjc.2015.38","article-title":"Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review","volume":"112","author":"Kimhofer","year":"2015","journal-title":"Br J Cancer"},{"issue":"2","key":"10.1016\/j.ebiom.2020.102699_bib0014","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jcmgh.2017.05.004","article-title":"Identification of the consistently altered metabolic targets in human hepatocellular carcinoma","volume":"4","author":"Nwosu","year":"2017","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"1","key":"10.1016\/j.ebiom.2020.102699_bib0015","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13046-018-0872-6","article-title":"Liver cancer cell lines distinctly mimic the metabolic gene expression pattern of the corresponding human tumours","volume":"37","author":"Nwosu","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"issue":"10","key":"10.1016\/j.ebiom.2020.102699_bib0016","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/nrc.2016.71","article-title":"From krebs to clinic: glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"10.1016\/j.ebiom.2020.102699_bib0017","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/bjc.2014.425","article-title":"Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts","volume":"111","author":"Chiu","year":"2014","journal-title":"Br J Cancer"},{"issue":"49","key":"10.1016\/j.ebiom.2020.102699_bib0018","doi-asserted-by":"crossref","first-page":"19345","DOI":"10.1073\/pnas.0709747104","article-title":"Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis","volume":"104","author":"DeBerardinis","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"10.1016\/j.ebiom.2020.102699_bib0019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002229","article-title":"Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia","volume":"7","author":"Kung","year":"2011","journal-title":"PLoS Genet"},{"issue":"1","key":"10.1016\/j.ebiom.2020.102699_bib0020","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cmet.2011.12.009","article-title":"Glucose-independent glutamine metabolism via tca cycling for proliferation and survival in b cells","volume":"15","author":"Le","year":"2012","journal-title":"Cell Metab"},{"issue":"7381","key":"10.1016\/j.ebiom.2020.102699_bib0021","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10602","article-title":"Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia","volume":"481","author":"Metallo","year":"2011","journal-title":"Nature"},{"issue":"7443","key":"10.1016\/j.ebiom.2020.102699_bib0022","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature12040","article-title":"Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway","volume":"496","author":"Son","year":"2013","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.ebiom.2020.102699_bib0023","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccr.2013.08.020","article-title":"Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target","volume":"24","author":"Timmerman","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ebiom.2020.102699_bib0024","article-title":"Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification","author":"Castven","year":"2018","journal-title":"Int J Cancer"},{"key":"10.1016\/j.ebiom.2020.102699_bib0025","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40170-016-0141-0","article-title":"The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells","volume":"4","author":"Battello","year":"2016","journal-title":"Cancer Metab"},{"issue":"9","key":"10.1016\/j.ebiom.2020.102699_bib0026","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s00204-015-1571-0","article-title":"RNAi in murine hepatocytes: the agony of choice\u2013a study of the influence of lipid-based transfection reagents on hepatocyte metabolism","volume":"89","author":"Bottger","year":"2015","journal-title":"Arch Toxicol"},{"issue":"20","key":"10.1016\/j.ebiom.2020.102699_bib0027","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1093\/nar\/gni179","article-title":"Evolving gene\/transcript definitions significantly alter the interpretation of genechip data","volume":"33","author":"Dai","year":"2005","journal-title":"Nucleic Acids Res"},{"issue":"21","key":"10.1016\/j.ebiom.2020.102699_bib0028","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.1073\/pnas.1016627108","article-title":"Pyruvate carboxylase is required for glutamine-independent growth of tumor cells","volume":"108","author":"Cheng","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"10.1016\/j.ebiom.2020.102699_bib0029","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.molcel.2014.09.026","article-title":"A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth","volume":"56","author":"Schell","year":"2014","journal-title":"Mol Cell"},{"issue":"19","key":"10.1016\/j.ebiom.2020.102699_bib0030","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.4161\/cc.21944","article-title":"Glutamine depletion and glucose depletion trigger growth inhibition via distinctive gene expression reprogramming","volume":"11","author":"Qie","year":"2012","journal-title":"Cell Cycle"},{"issue":"4","key":"10.1016\/j.ebiom.2020.102699_bib0031","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/cr.2015.33","article-title":"cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions","volume":"25","author":"Sun","year":"2015","journal-title":"Cell Res"},{"issue":"4","key":"10.1016\/j.ebiom.2020.102699_bib0032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005158","article-title":"Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis","volume":"11","author":"Tang","year":"2015","journal-title":"PLoS Genet"},{"issue":"12","key":"10.1016\/j.ebiom.2020.102699_bib0033","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/ng.3421","article-title":"NRF2 regulates serine biosynthesis in non-small cell lung cancer","volume":"47","author":"DeNicola","year":"2015","journal-title":"Nat Genet"},{"issue":"9","key":"10.1016\/j.ebiom.2020.102699_bib0034","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/ng.890","article-title":"Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis","volume":"43","author":"Locasale","year":"2011","journal-title":"Nat Genet"},{"issue":"8","key":"10.1016\/j.ebiom.2020.102699_bib0035","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1111\/liv.12778","article-title":"Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment","volume":"35","author":"Negri","year":"2015","journal-title":"Liver Int"},{"issue":"6","key":"10.1016\/j.ebiom.2020.102699_bib0036","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1136\/gutjnl-2018-316408","article-title":"Molecular predictors of prevention of recurrence in hcc with sorafenib as adjuvant treatment and prognostic factors in the phase 3 storm trial","volume":"68","author":"Pinyol","year":"2019","journal-title":"Gut"},{"issue":"7539","key":"10.1016\/j.ebiom.2020.102699_bib0037","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nature13981","article-title":"Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells","volume":"518","author":"Carey","year":"2015","journal-title":"Nature"},{"issue":"16","key":"10.1016\/j.ebiom.2020.102699_bib0038","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1158\/0008-5472.CAN-13-0308","article-title":"Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics","volume":"73","author":"Huang","year":"2013","journal-title":"Cancer Res"},{"issue":"6","key":"10.1016\/j.ebiom.2020.102699_bib0039","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nbt.2530","article-title":"Heterogeneity of tumor-induced gene expression changes in the human metabolic network","volume":"31","author":"Hu","year":"2013","journal-title":"Nat Biotechnol"},{"issue":"5","key":"10.1016\/j.ebiom.2020.102699_bib0040","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1053\/j.gastro.2017.12.022","article-title":"Hedgehog-YAP signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells","volume":"154","author":"Du","year":"2018","journal-title":"Gastroenterology"},{"issue":"7381","key":"10.1016\/j.ebiom.2020.102699_bib0041","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nature10642","article-title":"Reductive carboxylation supports growth in tumour cells with defective mitochondria","volume":"481","author":"Mullen","year":"2011","journal-title":"Nature"},{"issue":"20","key":"10.1016\/j.ebiom.2020.102699_bib0042","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1038\/onc.2014.207","article-title":"Blocking anaplerotic entry of glutamine into the tca cycle sensitizes K-Ras mutant cancer cells to cytotoxic drugs","volume":"34","author":"Saqcena","year":"2015","journal-title":"Oncogene"},{"issue":"2","key":"10.1016\/j.ebiom.2020.102699_bib0043","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cmet.2011.12.015","article-title":"The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type","volume":"15","author":"Yuneva","year":"2012","journal-title":"Cell Metab"},{"issue":"7650","key":"10.1016\/j.ebiom.2020.102699_bib0044","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature22056","article-title":"Modulating the therapeutic response of tumours to dietary serine and glycine starvation","volume":"544","author":"Maddocks","year":"2017","journal-title":"Nature"},{"issue":"7360","key":"10.1016\/j.ebiom.2020.102699_bib0045","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature10350","article-title":"Functional genomics reveal that the serine synthesis pathway is essential in breast cancer","volume":"476","author":"Possemato","year":"2011","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.ebiom.2020.102699_bib0046","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1053\/j.gastro.2017.01.015","article-title":"Metabolomic identification of subtypes of nonalcoholic steatohepatitis","volume":"152","author":"Alonso","year":"2017","journal-title":"Gastroenterology"},{"issue":"5","key":"10.1016\/j.ebiom.2020.102699_bib0047","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1073\/pnas.1523434113","article-title":"Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated hcc patient","volume":"113","author":"Dazert","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ebiom.2020.102699_bib0048","article-title":"Molecular predictors of prevention of recurrence in hcc with sorafenib as adjuvant treatment and prognostic factors in the phase 3 storm trial","author":"Pinyol","year":"2018","journal-title":"Gut"},{"issue":"10","key":"10.1016\/j.ebiom.2020.102699_bib0049","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/nm.3955","article-title":"Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in t cell acute lymphoblastic leukemia","volume":"21","author":"Herranz","year":"2015","journal-title":"Nat Med"},{"issue":"10","key":"10.1016\/j.ebiom.2020.102699_bib0050","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/ncb3410","article-title":"Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation","volume":"18","author":"Pan","year":"2016","journal-title":"Nat Cell Biol"},{"issue":"15","key":"10.1016\/j.ebiom.2020.102699_bib0051","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.1158\/1078-0432.CCR-16-3118","article-title":"Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro","volume":"23","author":"Rebouissou","year":"2017","journal-title":"Clin Cancer Res"}],"container-title":["EBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396420300748?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396420300748?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:32:20Z","timestamp":1778873540000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396420300748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":51,"alternative-id":["S2352396420300748"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2020.102699","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance","name":"articletitle","label":"Article Title"},{"value":"EBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2020.102699","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"102699"}}