{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:41:59Z","timestamp":1791895319781,"version":"4.3.4"},"reference-count":73,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100011221","name":"School of Medicine, University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1016\/j.canlet.2019.11.013","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T12:01:12Z","timestamp":1573646472000},"page":"134-140","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":88,"special_numbering":"C","title":["Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities"],"prefix":"10.1016","volume":"470","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-7665","authenticated-orcid":false,"given":"Alyncia D.","family":"Robinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lisa","family":"Eich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooryanarayana","family":"Varambally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2019.11.013_bib1","first-page":"7","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"Ca - Cancer J. Clin."},{"key":"10.1016\/j.canlet.2019.11.013_bib2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.canlet.2019.11.013_bib3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/nyas.12956","article-title":"One-carbon metabolism and epigenetics: understanding the specificity","volume":"1363","author":"Mentch","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.canlet.2019.11.013_bib4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.mcna.2016.09.013","article-title":"Megaloblastic anemias: nutritional and other causes","volume":"101","author":"Green","year":"2017","journal-title":"Med. Clin. N. Am."},{"key":"10.1016\/j.canlet.2019.11.013_bib5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1158\/1541-7786.MCR-16-0317","article-title":"Metabolic reprogramming by folate restriction leads to a less aggressive cancer phenotype","volume":"15","author":"Ashkavand","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib6","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1056\/NEJM198311033091805","article-title":"The pharmacology and clinical use of methotrexate","volume":"309","author":"Jolivet","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2019.11.013_bib7","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nature25460","article-title":"Mitochondrial translation requires folate-dependent tRNA methylation","volume":"554","author":"Morscher","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2019.11.013_bib8","doi-asserted-by":"crossref","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":"10.1016\/j.canlet.2019.11.013_bib9","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/bjc.2017.118","article-title":"One-carbon metabolism in cancer","volume":"116","author":"Newman","year":"2017","journal-title":"Br. J. Canc."},{"key":"10.1016\/j.canlet.2019.11.013_bib10","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ccell.2019.02.014","article-title":"Vulnerabilities in lethal prostate cancer","volume":"35","author":"Gao","year":"2019","journal-title":"Cancer Cell"},{"key":"10.1016\/j.canlet.2019.11.013_bib11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/00365521.2017.1407440","article-title":"The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell carcinoma","volume":"53","author":"Yang","year":"2018","journal-title":"Scand. J. Gastroenterol."},{"key":"10.1016\/j.canlet.2019.11.013_bib12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1158\/2159-8290.CD-16-0611","article-title":"Adaptive reprogramming of de novo pyrimidine synthesis is a metabolic vulnerability in triple-negative breast cancer","volume":"7","author":"Brown","year":"2017","journal-title":"Cancer Discov."},{"key":"10.1016\/j.canlet.2019.11.013_bib13","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.neo.2018.07.006","article-title":"A role for de novo purine metabolic enzyme PAICS in bladder cancer progression,","volume":"20","author":"Chakravarthi","year":"2018","journal-title":"Neoplasia"},{"key":"10.1016\/j.canlet.2019.11.013_bib14","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.4161\/cc.6390","article-title":"Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells","volume":"7","author":"Mannava","year":"2008","journal-title":"Cell Cycle"},{"key":"10.1016\/j.canlet.2019.11.013_bib15","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1021\/ar0000509","article-title":"Inhibitors of de novo nucleotide biosynthesis as drugs","volume":"35","author":"Christopherson","year":"2002","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib16","doi-asserted-by":"crossref","first-page":"23955","DOI":"10.18632\/oncotarget.15053","article-title":"One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy","volume":"8","author":"Shuvalov","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2019.11.013_bib17","series-title":"Purine bases can Be synthesized de Novo or recycled by salvage pathways, Biochemistry","author":"Berg","year":"2002"},{"key":"10.1016\/j.canlet.2019.11.013_bib18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.canlet.2014.01.017","article-title":"Nucleotide metabolism, oncogene-induced senescence and cancer","volume":"356","author":"Aird","year":"2015","journal-title":"Cancer Lett."},{"key":"10.1016\/j.canlet.2019.11.013_bib19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jgg.2015.04.004","article-title":"Pyrimidine Metabolism: Dynamic and Versatile Pathways In pathogens and cellular development","volume":"42","author":"Garavito","year":"2015","journal-title":"J. Genet. Genom."},{"key":"10.1016\/j.canlet.2019.11.013_bib20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: how does it benefit cancer cells?,","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.canlet.2019.11.013_bib21","doi-asserted-by":"crossref","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":"10.1016\/j.canlet.2019.11.013_bib22","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2011.07.014","article-title":"Metabolic flux and the regulation of mammalian cell growth","volume":"14","author":"Locasale","year":"2011","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2019.11.013_bib23","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJM194806032382301","article-title":"Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid","volume":"238","author":"Farber","year":"1948","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2019.11.013_bib24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3181\/00379727-93-22757","article-title":"Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma","volume":"93","author":"Hertz","year":"1956","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"10.1016\/j.canlet.2019.11.013_bib25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-fluorouracil: mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2019.11.013_bib26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2014.07.041","article-title":"Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer","volume":"741","author":"de Sousa Cavalcante","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.canlet.2019.11.013_bib27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2165\/00003495-199754030-00009","article-title":"Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer","volume":"54","author":"Noble","year":"1997","journal-title":"Drugs"},{"key":"10.1016\/j.canlet.2019.11.013_bib28","first-page":"2989","article-title":"DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer","volume":"33","author":"Gnyszka","year":"2013","journal-title":"Anticancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1124\/mol.114.095679","article-title":"S-Adenosylmethionine and methylthioadenosine inhibit beta-catenin signaling by multiple mechanisms in liver and colon cancer","volume":"87","author":"Li","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.canlet.2019.11.013_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2017.05.107","article-title":"Identification of AHCY inhibitors using novel high-throughput mass spectrometry","volume":"491","author":"Uchiyama","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.canlet.2019.11.013_bib31","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/jcb.25782","article-title":"Therapeutic potential of small molecule inhibitors","volume":"118","author":"Khera","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.canlet.2019.11.013_bib32","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nchembio1207-739","article-title":"Recognizing and exploiting differences between RNAi and small-molecule inhibitors","volume":"3","author":"Weiss","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.canlet.2019.11.013_bib33","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.cmet.2016.04.016","article-title":"Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway","volume":"23","author":"Ducker","year":"2016","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2019.11.013_bib34","doi-asserted-by":"crossref","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":"10.1016\/j.canlet.2019.11.013_bib35","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.AM2018-3516","article-title":"Abstract 3516: discovery of novel SHMT small molecule inhibitors for cancer treatment","volume":"78","author":"Bartosik","year":"2018","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib36","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.AM2017-442","article-title":"Abstract 442: small molecule inhibitors of SHMT1\/2 validate serine metabolism as a target in the treatment of c-Myc positive solid tumors","volume":"77","author":"Rzymski","year":"2017","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib37","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1158\/0008-5472.CAN-16-1476","article-title":"Crystal structure of the emerging cancer target MTHFD2 in complex with a substrate-based inhibitor","volume":"77","author":"Gustafsson","year":"2017","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib38","article-title":"Modulation of redox homeostasis by inhibition of MTHFD2 in colorectal cancer: mechanisms and therapeutic implications","author":"Ju","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.canlet.2019.11.013_bib39","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0021-9258(17)31261-9","article-title":"A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis","volume":"264","author":"Beardsley","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2019.11.013_bib40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00194536","article-title":"A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid","volume":"14","author":"Laohavinij","year":"1996","journal-title":"Investig. New Drugs"},{"key":"10.1016\/j.canlet.2019.11.013_bib41","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1054\/bjoc.2000.1601","article-title":"Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034","volume":"84","author":"Bissett","year":"2001","journal-title":"Br. J. Canc."},{"key":"10.1016\/j.canlet.2019.11.013_bib42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00194533","article-title":"AG2034: a novel inhibitor of glycinamide ribonucleotide formyltransferase","volume":"14","author":"Boritzki","year":"1996","journal-title":"Investig. New Drugs"},{"key":"10.1016\/j.canlet.2019.11.013_bib43","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.sjbs.2014.11.008","article-title":"In silico analysis of glycinamide ribonucleotide transformylase inhibition by PY873, PY899 and DIA","volume":"24","author":"Batool","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"10.1016\/j.canlet.2019.11.013_bib44","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1021\/jm0601147","article-title":"Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase","volume":"49","author":"DeMartino","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.canlet.2019.11.013_bib45","doi-asserted-by":"crossref","first-page":"11038","DOI":"10.1016\/S0021-9258(19)49872-4","article-title":"Antifolates induce inhibition of amido phosphoribosyltransferase in leukemia cells","volume":"267","author":"Sant","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2019.11.013_bib46","doi-asserted-by":"crossref","first-page":"50555","DOI":"10.1074\/jbc.M406801200","article-title":"Crystal structure of avian aminoimidazole-4-carboxamide ribonucleotide transformylase in complex with a novel non-folate inhibitor identified by virtual ligand screening","volume":"279","author":"Xu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2019.11.013_bib47","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1002\/cbic.201200279","article-title":"Targeting tumour proliferation with a small-molecule inhibitor of AICAR transformylase homodimerization","volume":"13","author":"Spurr","year":"2012","journal-title":"Chembiochem"},{"key":"10.1016\/j.canlet.2019.11.013_bib48","doi-asserted-by":"crossref","first-page":"9599","DOI":"10.1021\/acs.jmedchem.7b01046","volume":"60","author":"Fales","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.canlet.2019.11.013_bib49","doi-asserted-by":"crossref","first-page":"15458","DOI":"10.1038\/s41598-018-33453-4","article-title":"Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models","volume":"8","author":"Brooks","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2019.11.013_bib50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/pros.23243","article-title":"Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer","volume":"77","author":"Chakravarthi","year":"2017","journal-title":"The Prostate"},{"key":"10.1016\/j.canlet.2019.11.013_bib51","doi-asserted-by":"crossref","first-page":"23445","DOI":"10.18632\/oncotarget.4352","article-title":"Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer","volume":"6","author":"Goswami","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2019.11.013_bib52","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40659-018-0172-9","article-title":"Knockdown of PAICS inhibits malignant proliferation of human breast cancer cell lines","volume":"51","author":"Meng","year":"2018","journal-title":"Biol. Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib53","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.celrep.2017.10.029","article-title":"The mTORC1 signaling network senses changes in cellular purine nucleotide levels,","volume":"21","author":"Hoxhaj","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.canlet.2019.11.013_bib54","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.7150\/jca.14835","article-title":"Dihydroorotate dehydrogenase inhibitors target c-myc and arrest melanoma, myeloma and lymphoma cells at S-phase","volume":"8","author":"Dorasamy","year":"2017","journal-title":"J. Cancer"},{"key":"10.1016\/j.canlet.2019.11.013_bib55","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chembiol.2018.03.005","article-title":"Dependence on the pyrimidine biosynthetic enzyme DHODH is a synthetic lethal vulnerability in mutant KRAS-driven cancers","volume":"25","author":"Koundinya","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.canlet.2019.11.013_bib56","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s41467-018-03441-3","article-title":"A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage","volume":"9","author":"Ladds","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2019.11.013_bib57","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.biochi.2017.02.003","article-title":"Dihydroorotate dehydrogenase (DHODH) inhibitors affect ATP depletion, endogenous ROS and mediate S-phase arrest in breast cancer cells","volume":"135","author":"Mohamad Fairus","year":"2017","journal-title":"Biochimie"},{"key":"10.1016\/j.canlet.2019.11.013_bib58","first-page":"4648","article-title":"Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390)","volume":"49","author":"Arteaga","year":"1989","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2019.11.013_bib59","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1158\/1535-7163.MCT-08-0664","article-title":"Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis and diminishes proliferation of multiple myeloma cells","volume":"8","author":"Baumann","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.canlet.2019.11.013_bib60","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1097\/00000421-199312000-00014","article-title":"Multicenter phase II study of brequinar sodium in patients with advanced breast cancer","volume":"16","author":"Cody","year":"1993","journal-title":"Am. J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2019.11.013_bib61","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1124\/jpet.112.192203","article-title":"Vidofludimus inhibits colonic interleukin-17 and improves hapten-induced colitis in rats by a unique dual mode of action","volume":"342","author":"Fitzpatrick","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.canlet.2019.11.013_bib62","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0006-2952(96)00303-6","article-title":"Two activities of the immunosuppressive metabolite of leflunomide, A77 1726. Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylation","volume":"52","author":"Xu","year":"1996","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.canlet.2019.11.013_bib63","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4049\/jimmunol.160.2.846","article-title":"In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium","volume":"160","author":"Xu","year":"1998","journal-title":"J. Immunol."},{"key":"10.1016\/j.canlet.2019.11.013_bib64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1535-7163.MCT-18-0863","article-title":"Targeting of hematologic malignancies with PTC299, A novel potent inhibitor of dihydroorotate dehydrogenase with favorable pharmaceutical properties,","volume":"18","author":"Cao","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.canlet.2019.11.013_bib65","doi-asserted-by":"crossref","DOI":"10.1038\/s41375-019-0461-5","article-title":"The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies","author":"Christian","year":"2019","journal-title":"Leukemia"},{"key":"10.1016\/j.canlet.2019.11.013_bib66","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-110570","article-title":"Preliminary results of a phase 2a dose optimization study of ASLAN003 (DHODH inhibitor) in acute myeloid leukemia (AML) patients who are ineligible for standard therapy; early signs of activity","volume":"132","author":"Ting","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.canlet.2019.11.013_bib67","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nature11743","article-title":"Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells","volume":"493","author":"Maddocks","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2019.11.013_bib68","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"},{"key":"10.1016\/j.canlet.2019.11.013_bib69","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"10.1016\/j.canlet.2019.11.013_bib70","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"10.1016\/j.canlet.2019.11.013_bib71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1476-5586(04)80047-2","article-title":"ONCOMINE: a cancer microarray database and integrated data-mining platform","volume":"6","author":"Rhodes","year":"2004","journal-title":"Neoplasia"},{"key":"10.1016\/j.canlet.2019.11.013_bib72","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1593\/neo.07112","article-title":"Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles","volume":"9","author":"Rhodes","year":"2007","journal-title":"Neoplasia"},{"key":"10.1016\/j.canlet.2019.11.013_bib73","first-page":"649","article-title":"UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses, neoplasia (New York, N.Y","volume":"19","author":"Chandrashekar","year":"2017"}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383519305683?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383519305683?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T15:46:09Z","timestamp":1759592769000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383519305683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":73,"alternative-id":["S0304383519305683"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2019.11.013","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2019.11.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}