{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:21:57Z","timestamp":1790400117638,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T00:00:00Z","timestamp":1539302400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2018.01129","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T01:07:51Z","timestamp":1539306471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolic Characterization of Antifolate Responsiveness and Non-responsiveness in Malignant Pleural Mesothelioma Cells"],"prefix":"10.3389","volume":"9","author":[{"given":"Yuzo","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Miyashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibiki","family":"Udagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Umemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Yanagihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ochiai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Soga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Tsuchihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Makinoshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,10,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.tibs.2014.02.004","article-title":"Serine and glycine metabolism in cancer.","volume":"39","author":"Amelio","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"627","DOI":"10.4161\/cbt.11.7.14948","article-title":"Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity: current strategies.","volume":"11","author":"Bertino","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/ng.3520","article-title":"Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.","volume":"48","author":"Bueno","year":"2016","journal-title":"Nat. Genet."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/436409","article-title":"Thymidylate synthase as a predictive biomarker for pemetrexed response in NSCLC.","volume":"2013","author":"Bukhari","year":"2013","journal-title":"Lung Cancer Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism.","volume":"11","author":"Cairns","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nbt.2285","article-title":"Therapeutic targets in cancer cell metabolism and autophagy.","volume":"30","author":"Cheong","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.chest.2016.12.004","article-title":"Malignant mesothelioma biomarkers: from discovery to use in clinical practice for diagnosis, monitoring, screening, and treatment.","volume":"152","author":"Creaney","year":"2017","journal-title":"Chest"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.15252\/embj.201796438","article-title":"MYC and tumor metabolism: chicken and egg.","volume":"36","author":"Dejure","year":"2017","journal-title":"EMBO J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1158\/0008-5472.CAN-15-0751","article-title":"Gender-specific molecular and clinical features underlie malignant pleural mesothelioma.","volume":"76","author":"De Rienzo","year":"2016","journal-title":"Cancer Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"11404","DOI":"10.1073\/pnas.1706617114","article-title":"Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma.","volume":"114","author":"Ducker","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-carbon metabolism in health and disease.","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1016\/j.jtho.2016.05.020","article-title":"The genetic landscape of malignant pleural mesothelioma: results from massively parallel sequencing.","volume":"11","author":"Hylebos","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"B13","first-page":"2108","article-title":"Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas.","volume":"9","author":"Illei","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"5693","DOI":"10.1038\/sj.onc.1210383","article-title":"EGFR kinase domain mutations - functional impact and relevance for lung cancer therapy.","volume":"26","author":"Irmer","year":"2007","journal-title":"Oncogene"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1126\/science.1218595","article-title":"Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation.","volume":"336","author":"Jain","year":"2012","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nature14363","article-title":"SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance.","volume":"520","author":"Kim","year":"2015","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1126\/science.aad5214","article-title":"MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells.","volume":"351","author":"Kryukov","year":"2016","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.celrep.2014.04.045","article-title":"Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells.","volume":"7","author":"Labuschagne","year":"2014","journal-title":"Cell Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1126\/science.1193494","article-title":"The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.","volume":"330","author":"Levine","year":"2010","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1146\/annurev-pharmtox-011112-140341","article-title":"Tyrosine kinase inhibitors: views of selectivity, sensitivity, and clinical performance.","volume":"53","author":"Levitzki","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.jtho.2017.04.002","article-title":"Epidemiology of environmental exposure and malignant mesothelioma.","volume":"12","author":"Liu","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: meeting the metabolic requirements of cell proliferation.","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"37502","DOI":"10.18632\/oncotarget.16398","article-title":"Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma.","volume":"8","author":"Mairinger","year":"2017","journal-title":"Oncotarget"},{"key":"B24","doi-asserted-by":"publisher","first-page":"20813","DOI":"10.1074\/jbc.M114.575464","article-title":"Epidermal growth factor receptor (EGFR) signaling regulates global metabolic pathways in EGFR-mutated lung adenocarcinoma.","volume":"289","author":"Makinoshima","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1158\/0008-5472.CAN-17-2109","article-title":"Metabolic determinants of sensitivity to phosphatidylinositol 3-kinase pathway inhibitor in small-cell lung carcinoma.","volume":"78","author":"Makinoshima","year":"2018","journal-title":"Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.aad5944","article-title":"Disordered methionine metabolism in MTAP\/CDKN2A-deleted cancers leads to dependence on PRMT5.","volume":"351","author":"Mavrakis","year":"2016","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.tcb.2017.05.001","article-title":"Serine and functional metabolites in cancer.","volume":"27","author":"Newman","year":"2017","journal-title":"Trends Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature22379","article-title":"Nutrient acquisition strategies of mammalian cells.","volume":"546","author":"Palm","year":"2017","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"42466","DOI":"10.18632\/oncotarget.17198","article-title":"Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.","volume":"8","author":"Satoh","year":"2017","journal-title":"Oncotarget"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.1200\/JCO.2007.15.0375","article-title":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.","volume":"26","author":"Scagliotti","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e161","DOI":"10.1016\/S1470-2045(18)30100-1","article-title":"Novel therapies for malignant pleural mesothelioma.","volume":"19","author":"Scherpereel","year":"2018","journal-title":"Lancet Oncol."},{"key":"B32","first-page":"1116","article-title":"LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes.","volume":"57","author":"Shih","year":"1997","journal-title":"Cancer Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/cas.12085","article-title":"Cancer metabolism: key players in metabolic reprogramming.","volume":"104","author":"Soga","year":"2013","journal-title":"Cancer Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1021\/ac990976y","article-title":"Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry.","volume":"72","author":"Soga","year":"2000","journal-title":"Anal. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1021\/pr034020m","article-title":"Quantitative metabolome analysis using capillary electrophoresis mass spectrometry.","volume":"2","author":"Soga","year":"2003","journal-title":"J. Proteome Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"6224","DOI":"10.1021\/ac0202684","article-title":"Pressure-assisted capillary electrophoresis electrospray ionization mass spectrometry for analysis of multivalent anions.","volume":"74","author":"Soga","year":"2002","journal-title":"Anal. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the warburg effect: the metabolic requirements of cell proliferation.","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1002\/ijc.25002","article-title":"An orthotopic implantation mouse model of human malignant pleural mesothelioma for in vivo photon counting analysis and evaluation of the effect of S-1 therapy.","volume":"126","author":"Yanagihara","year":"2010","journal-title":"Int. J. Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/nrc.2016.81","article-title":"Serine and one-carbon metabolism in cancer.","volume":"16","author":"Yang","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"B41","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nrc.2017.42","article-title":"Novel insights into mesothelioma biology and implications for therapy.","volume":"17","author":"Yap","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.cell.2011.11.050","article-title":"Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis.","volume":"148","author":"Zhang","year":"2012","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7431","DOI":"10.1038\/sj.onc.1206946","article-title":"Resistance to antifolates.","volume":"22","author":"Zhao","year":"2003","journal-title":"Oncogene"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01129\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T01:07:56Z","timestamp":1539306476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01129\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,12]]},"references-count":43,"alternative-id":["10.3389\/fphar.2018.01129"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2018.01129","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,12]]},"article-number":"1129"}}