{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:33:29Z","timestamp":1773693209781,"version":"3.50.1"},"reference-count":138,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["NIH\/NCI R01CA 213987"],"award-info":[{"award-number":["NIH\/NCI R01CA 213987"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. The initiation and progression of CRC is a multi-step process that proceeds via precursor lesions to carcinoma, with each stage characterized by its distinct molecular and tissue microenvironment changes. Precursor lesions of CRC, aberrant crypt foci, and adenoma exhibit drastic changes in genetic, transcriptomic, and proteomic profiles compared to normal tissue. The identification of these changes is essential and provides further validation as an initiator or promoter of CRC and, more so, as lesion-specific druggable molecular targets for the precision chemoprevention of CRC. Mutated\/dysregulated signaling (adenomatous polyposis coli, \u03b2-catenin, epidermal growth factor receptor, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), tumor protein53, Akt, etc.), inflammatory (cyclooxygenase-2, microsomal prostaglandin E synthase-1, inducible nitric oxide synthase, and other pro-inflammatory mediators), and metabolic\/growth factor (fatty acid synthase, \u03b2-Hydroxy \u03b2-methylglutaryl-CoA reductase, and ornithine decarboxylase) related targets are some of the well-characterized molecular targets in the precision chemoprevention of CRC. In this review, we discuss precursor-lesion specific targets of CRC and the current status of pre-clinical studies regarding clinical interventions and combinations for better efficacy and safety toward future precision clinical chemoprevention. In addition, we provide a brief discussion on the usefulness of secondary precision chemopreventive targets for tertiary precision chemoprevention to improve the disease-free and overall survival of advanced stage CRC patients.<\/jats:p>","DOI":"10.3390\/ijms21249609","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"9609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Molecular Targets in Precision Chemoprevention of Colorectal Cancer: An Update from Pre-Clinical to Clinical Trials"],"prefix":"10.3390","volume":"21","author":[{"given":"Nagendra S.","family":"Yarla","sequence":"first","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Medical Oncology, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-4095","authenticated-orcid":false,"given":"Venkateshwar","family":"Madka","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Medical Oncology, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gopal","family":"Pathuri","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Medical Oncology, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinthalapally V.","family":"Rao","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Medical Oncology, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"VA Medical Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","unstructured":"The American Cancer Society Journal, CA: A Cancer Journal for Clinicians (2020, October 10). Cancer Facts & Figures. Available online: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/colorectal-cancer-facts-and-figures\/colorectal-cancer-facts-and-figures-2020-2022.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1745-7254.2008.00742.x","article-title":"Molecular markers and targets for colorectal cancer prevention","volume":"29","author":"Janakiram","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00428-016-1956-3","article-title":"Molecular pathological classification of colorectal cancer","volume":"469","author":"Ibrahim","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S0959-8049(02)00040-0","article-title":"The APC gene in colorectal cancer","volume":"38","author":"Fodde","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3748\/wjg.v7.i3.352","article-title":"APC and K-ras gene mutation in aberrant crypt foci of human colon","volume":"7","author":"Yuan","year":"2001","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41598-017-18421-8","article-title":"Beta-catenin cleavage enhances transcriptional activation","volume":"8","author":"Goretsky","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1158\/0008-5472.CAN-06-3861","article-title":"Frequent mutation of Apc gene in rat colon tumors and mucin-depleted foci, preneoplastic lesions in experimental colon carcinogenesis","volume":"67","author":"Femia","year":"2007","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Femia, A.P., Piero, D., Maddalena, S., and Giovanna, C. (2013). Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazine-induced rat colon carcinogenesis: Correlation with nuclear \u03b2-catenin. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-48"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.biopha.2018.11.082","article-title":"Therapeutic Potential of Targeting the Wnt\/\u03b2-catenin Signaling Pathway in Colorectal Cancer","volume":"110","author":"Xiaofei","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0065-2423(10)51004-7","article-title":"EGFR and KRAS in colorectal cancer","volume":"51","author":"Markman","year":"2010","journal-title":"Adv. Clin. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1016\/S0305-7372(10)70021-9","article-title":"Prognostic vs predictive molecular biomarkers in colorectal cancer: Is KRAS and BRAF wild type status required for anti-EGFR therapy?","volume":"36","author":"Rizzo","year":"2010","journal-title":"Cancer Treat. Rev."},{"key":"ref_12","first-page":"83","article-title":"Mutant KRAS in aberrant crypt foci (ACF): Initiation of colorectal cancer?","volume":"1756","author":"Pretlow","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/ijc.23065","article-title":"K-ras mutations and mucin profile in preneoplastic lesions and colon tumors induced in rats by 1,2-dimethylhydrazine","volume":"122","author":"Femia","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1093\/carcin\/21.7.1319","article-title":"Altered expression of beta-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis","volume":"21","author":"Takahashi","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/MCG.0000000000000809","article-title":"Clinical Predictors for KRAS Codon 13 Mutations in Patients with Colorectal Cancer","volume":"52","author":"Kwak","year":"2018","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/ijc.28106","article-title":"KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy","volume":"133","author":"Valtorta","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1053\/gast.1996.v110.pm8566583","article-title":"High levels of transforming growth factor beta 1 in patients with colorectal cancer: Association with disease progression","volume":"110","author":"Tsushima","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_18","first-page":"401","article-title":"SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and mice","volume":"42","author":"Szigeti","year":"2012","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jcmgh.2018.05.006","article-title":"Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer","volume":"6","author":"Means","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00535-006-1801-6","article-title":"Colorectal cancer: Genetics of development and metastasis","volume":"41","author":"Takayama","year":"2006","journal-title":"J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3748\/wjg.v21.i1.84","article-title":"p53 mutations in colorectal cancer- molecular pathogenesis and pharmacological reactivation","volume":"21","author":"Xiao","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/0016-5085(95)90071-3","article-title":"Frequent and characteristic K-ras activation and absence of p53 protein accumulation in aberrant crypt foci of the colon","volume":"108","author":"Yamashita","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/(SICI)1096-9896(199603)178:3<259::AID-PATH473>3.0.CO;2-4","article-title":"K-ras and p53 mutations in human colorectal aberrant crypt foci","volume":"178","author":"Losi","year":"1996","journal-title":"J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1093\/carcin\/bgm134","article-title":"Loss of p53 enhances the induction of colitis-associated neoplasia by dextran sulfate sodium","volume":"28","author":"Chang","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.humpath.2019.04.013","article-title":"Targeted mutational analysis of inflammatory bowel disease-associated colorectal cancers","volume":"89","author":"Alpert","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22175","DOI":"10.18632\/oncotarget.14549","article-title":"KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: A meta-analysis","volume":"8","author":"Du","year":"2017","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1158\/0008-5472.CAN-08-1610","article-title":"Suppression of familial adenomatous polyposis by CP-31398, a TP53 modulator, in APCmin\/+ mice","volume":"68","author":"Rao","year":"2008","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.2174\/1389450120666190618123846","article-title":"PI3K\/Akt\/mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence","volume":"20","author":"Narayanankutty","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3816\/CCC.2007.n.034","article-title":"Activation of the serine\/threonine protein kinase AKT during the progression of colorectal neoplasia","volume":"6","author":"Saglam","year":"2007","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/carcin\/23.1.201","article-title":"AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis","volume":"23","author":"Roy","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1158\/1078-0432.CCR-14-3281","article-title":"Phase II Study of the AKT Inhibitor MK-2206 plus Erlotinib in Patients with Advanced Non-Small Cell Lung Cancer Who Previously Progressed on Erlotinib","volume":"21","author":"Lara","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_32","first-page":"3785","article-title":"Expression of cyclooxygenase-1 and -2 in human colorectal cancer","volume":"55","author":"Sano","year":"1995","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35094017","article-title":"Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2","volume":"1","author":"Gupta","year":"2001","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ijc.24417","article-title":"Mucin-depleted foci show strong activation of inflammatory markers in 1,2-dimethylhydrazine-induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate","volume":"125","author":"Femia","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.31557\/APJCP.2019.20.6.1675","article-title":"Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients","volume":"20","author":"Negi","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Roelofs, H.M., Te Morsche, R.H., van Heumen, B.W., Nagengast, F.M., and Peters, W.H. (2014). Over-expression of COX-2 mRNA in colorectal cancer. BMC Gastroenterol., 2.","DOI":"10.1186\/1471-230X-14-1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1590\/0102-6720201700020008","article-title":"Polymorphism of the COX-2 gene and susceptibility to colon and rectal cancer","volume":"30","author":"Cossiolo","year":"2017","journal-title":"Arq. Bras. Cir. Dig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1053\/j.gastro.2019.06.047","article-title":"Chemoprevention of Colorectal Cancer","volume":"158","author":"Katona","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mohammed, A., Yarla, N.S., Madka, V., and Rao, C.V. (2018). Clinically Relevant Anti-Inflammatory Agents for Chemoprevention of Colorectal Cancer: New Perspectives. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082332"},{"key":"ref_40","first-page":"3","article-title":"Cancer prevention and screening: The next step in the era of precision medicine","volume":"28","author":"Umar","year":"2019","journal-title":"NPJ Precis Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nrc.2016.4","article-title":"Aspirin and colorectal cancer: The promise of precision chemoprevention","volume":"16","author":"Drew","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1056\/NEJMoa067208","article-title":"Aspirin and the risk of colorectal cancer in relation to the expression of COX-2","volume":"356","author":"Chan","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"dju016","DOI":"10.1093\/jnci\/dju016","article-title":"A prospective study of macrophage inhibitory cytokine-1 (MIC-1\/GDF15) and risk of colorectal cancer","volume":"106","author":"Mehta","year":"2014","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"JAMA United States Preventative Services Task Force (2016). Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA, 315, 2564\u20132575.","DOI":"10.1001\/jama.2016.5989"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1158\/0008-5472.CAN-07-6100","article-title":"Genetic Deletion of mPGES-1 Suppresses Intestinal Tumorigenesis","volume":"68","author":"Nakanishi","year":"2008","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1038\/onc.2011.472","article-title":"Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis","volume":"31","author":"Sasaki","year":"2012","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"75","DOI":"10.5217\/ir.2017.15.1.75","article-title":"15-Hydroxyprostaglandin dehydrogenase as a marker in colon carcinogenesis: Analysis of the prostaglandin pathway in human colonic tissue","volume":"15","author":"Yang","year":"2017","journal-title":"Intest. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19396","DOI":"10.1074\/jbc.M213290200","article-title":"Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis","volume":"278","author":"Kamei","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1158\/1078-0432.CCR-07-4631","article-title":"Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model","volume":"14","author":"Melstrom","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00384-010-0980-z","article-title":"Overexpression of 5-lipoxygenase in sporadic colonic adenomas and a possible new aspect of colon carcinogenesis","volume":"25","author":"Wasilewicz","year":"2010","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_51","first-page":"6307","article-title":"Lipoxygenase modulation to reverse carcinogenesis","volume":"61","author":"Shureiqi","year":"2001","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1349-7006.2004.tb03235.x","article-title":"Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents","volume":"95","author":"Takahashi","year":"2004","journal-title":"Cancer Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0002-9440(10)63876-X","article-title":"Inducible nitric oxide synthase expression in human colorectal cancer: Correlation with tumor angiogenesis","volume":"162","author":"Cianchi","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1600-0463.2009.02569.x","article-title":"Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer","volume":"118","author":"Zafirellis","year":"2010","journal-title":"APMIS"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/ijc.29892","article-title":"Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15-hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis-associated cancer","volume":"138","author":"Kangwan","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3393\/jksc.2012.28.5.253","article-title":"Prognostic implication of 15-hydroxyprostaglandin dehydrogenase down-regulation in patients with colorectal cancer","volume":"28","author":"Kang","year":"2012","journal-title":"J. Korean Soc. Coloproctol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1158\/1535-7163.MCT-13-0378","article-title":"Embelin reduces colitis-associated tumorigenesis through limiting IL-6\/STAT3 signaling","volume":"13","author":"Dai","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, M.X., Bi, X.Y., Huang, Z., Zhao, J.J., Han, Y., Li, Z.Y., Zhang, Y.F., Li, Y., Chen, X., and Hu, X.H. (2015). Prognostic role of phospho-STAT3 in patients with cancers of the digestive system: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127356"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17376","DOI":"10.1038\/srep17376","article-title":"Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1","volume":"5","author":"Sasaki","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1158\/1055-9965.EPI-05-0804","article-title":"Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps","volume":"15","author":"Poole","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_61","first-page":"518","article-title":"Altered eicosanoid levels in human colon cancer","volume":"122","author":"Rigas","year":"1993","journal-title":"J. Lab. Clin. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/jnci\/djs187","article-title":"Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice","volume":"104","author":"Zuo","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1096\/fj.14-264515","article-title":"15-Lipoxygenase-1 suppression of colitis-associated colon cancer through inhibition of the IL-6\/STAT3 signaling pathway","volume":"29","author":"Mao","year":"2015","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.prostaglandins.2017.01.002","article-title":"ALOX15 as a suppressor of inflammation and cancer: Lost in the link","volume":"132","author":"Tian","year":"2017","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1093\/carcin\/20.9.1709","article-title":"APC-dependent changes in expression of genes influencing polyamine metabolism, and consequences for gastrointestinal carcinogenesis, in the Min mouse","volume":"20","author":"Erdman","year":"1999","journal-title":"Carcinogenesis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5387\/fms.53.1","article-title":"Ornithine decarboxylase activity as a prognostic marker for colorectal cancer","volume":"53","author":"Hoshino","year":"2007","journal-title":"Fukushima J. Med. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1158\/1078-0432.CCR-09-0592","article-title":"Associations of a polymorphism in the ornithine decarboxylase gene with colorectal cancer survival","volume":"15","author":"Zell","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_68","first-page":"141","article-title":"Relationship of ornithinedecarboxylase activity and human colon tumorigenesis","volume":"24","author":"Takami","year":"1994","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ebiom.2016.07.019","article-title":"Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Histone Deacetylase as a Therapy for Colorectal Cancer","volume":"10","author":"Wei","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1093\/carcin\/bgu068","article-title":"Olive oil and omega-3 polyunsaturated fatty acids suppress intestinal polyp growth by modulating the apoptotic process in ApcMin\/+ mice","volume":"35","author":"Barone","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1746-1596-9-78","article-title":"HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome","volume":"9","author":"Bengtsson","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1158\/1055-9965.EPI-14-0026","article-title":"Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: Modulation by obesity and gender","volume":"23","author":"Cruz","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/ijc.24356","article-title":"Increased expression of fatty acid synthase in human aberrant crypt foci: Possible target for colorectal cancer prevention","volume":"125","author":"Kearney","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1158\/1940-6207.CAPR-11-0188","article-title":"Selective PGE(2) suppression inhibits colon carcinogenesis and modifies local mucosal immunity","volume":"4","author":"Nakanishi","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_75","first-page":"895","article-title":"Association of 5-lipoxygenase expression and clinicopathological factors in colorectal carcinoma","volume":"16","author":"Li","year":"2013","journal-title":"Zhonghua Wei Chang. Wai Ke Za Zhi"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gounaris, E., Heiferman, M.J., Heiferman, J.R., Shrivastav, M., Vitello, D., Blatner, N.R., Knab, L.M., Phillips, J.D., Cheon, E.C., and Grippo, P.J. (2015). Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121402"},{"key":"ref_77","first-page":"1748","article-title":"Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells","volume":"63","author":"Cutler","year":"2003","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1038\/sj.onc.1208883","article-title":"Hypermethylation of the prostacyclin synthase (PTGIS) promoter is a frequent event in colorectal cancer and associated with aneuploidy","volume":"24","author":"Frigola","year":"2005","journal-title":"Oncogene"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1158\/1055-9965.EPI-17-0573","article-title":"The expression of Cox-2 and 15-PGDH in pre-treatment adenomas provides predictive information in patients treated with celecoxib for prevention of colorectal adenomas","volume":"27","author":"Wang","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9331","DOI":"10.1158\/0008-5472.CAN-08-2893","article-title":"Repression of 15-hydroxyprostaglandin dehydrogenase involves histone deacetylase 2 and snail in colorectal cancer","volume":"68","author":"Backlund","year":"2008","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1073\/pnas.1804000116","article-title":"Aspirin-triggered proresolving mediators stimulate resolution in cancer","volume":"116","author":"Gilligan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1002\/jcb.23174","article-title":"15-lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma","volume":"112","author":"Cimen","year":"2011","journal-title":"J. Cell Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1111\/j.1349-7006.2009.01313.x","article-title":"15-Lipoxygenase-1 expression suppresses the invasive properties of colorectal carcinoma cell lines HCT-116 and HT-29","volume":"100","author":"Cimen","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/cpr.12267","article-title":"Interplay between 15-lipoxygenase-1 and metastasis-associated antigen 1 in the metastatic potential of colorectal cancer","volume":"49","author":"Konu","year":"2016","journal-title":"Cell Prolif."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cellsig.2017.07.022","article-title":"15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1","volume":"39","author":"Yener","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1111\/j.1440-1746.2007.04842.x","article-title":"The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds","volume":"22","author":"Yoshinaga","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.3748\/wjg.v9.i6.1246","article-title":"Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma-carcinoma sequence","volume":"9","author":"Xu","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2010.07.023","article-title":"Regular exercise reduces colon tumorigenesis associated with suppression of iNOS","volume":"399","author":"Aoi","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0891-5849(02)01363-1","article-title":"Nitric oxide in cancer and chemoprevention","volume":"34","author":"Hofseth","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","first-page":"815","article-title":"Is inducible nitric oxide synthase a target for chemoprevention?","volume":"2","author":"Crowell","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_91","first-page":"8357","article-title":"Suppression of intestinal polyposis in ApcMin\/+ mice by inhibiting nitric oxide production","volume":"61","author":"Ahn","year":"2001","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.niox.2018.12.008","article-title":"Nitric oxide synthase inhibitors 1400W and L-NIO inhibit angiogenesis pathway of colorectal cancer","volume":"83","author":"Gao","year":"2019","journal-title":"Nitric Oxide."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2174\/138945008784221116","article-title":"Signaling molecules: The pathogenic role of the IL-6\/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer","volume":"9","author":"Atreya","year":"2008","journal-title":"Curr. Drug Targets"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3892\/or.2013.2858","article-title":"Activation of the JAK-STAT3 pathway is associated with the growth of colorectal carcinoma cells","volume":"31","author":"Wei","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/mc.22168","article-title":"Adoptive transfer of regulatory T cells promotes intestinal tumorigenesis and is associated with decreased NK cells and IL-22 binding protein","volume":"54","author":"Janakiram","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/carcin\/bgy009","article-title":"Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation","volume":"39","author":"Chen","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/ijc.28779","article-title":"Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice","volume":"135","author":"Sasaki","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40001-017-0283-8","article-title":"Colorectal cancer-infiltrating T lymphocytes display a distinct chemokine receptor expression profile","volume":"22","author":"Kadivar","year":"2017","journal-title":"Eur. J. Med. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7929","DOI":"10.1007\/s13277-014-2069-8","article-title":"C-X-C chemokine receptor type 5 gene polymorphism affects gene expression in CD4+ T cells and is associated with increased risk of colorectal cancer","volume":"35","author":"Xing","year":"2014","journal-title":"Tumour. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"48335","DOI":"10.18632\/oncotarget.10227","article-title":"Blockade of the chemokine receptor, CCR5, reduces the growth of orthotopically injected colon cancer cells via limiting cancer-associated fibroblast accumulation","volume":"7","author":"Tanabe","year":"2016","journal-title":"Oncotarget"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ccell.2016.03.005","article-title":"Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients","volume":"29","author":"Halama","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1158\/1541-7786.MCR-18-0199","article-title":"De Novo Fatty Acid Synthesis-Driven Sphingolipid Metabolism Promotes Metastatic Potential of Colorectal Cancer","volume":"17","author":"Jafari","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_103","unstructured":"Yekaterina, Y., Piotr, G.R., Tianyan, G., Eun, Y.L., Heidi, L.W., Timothy, S.H., George, K., and Mark, B.E. (2016, January 16\u201320). Evaluation of small-molecule FASN inhibitors in preclinical models of colorectal cancer. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research, New Orleans, LA, USA."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"24787","DOI":"10.18632\/oncotarget.25361","article-title":"Preclinical evaluation of novel fatty acid synthase inhibitors in primary colorectal cancer cells and a patient-derived xenograft model of colorectal cancer","volume":"9","author":"Zaytseva","year":"2018","journal-title":"Oncotarget"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1007\/s13277-013-1510-8","article-title":"Fatty acid synthase (FASN) levels in serum of colorectal cancer patients: Correlation with clinical outcomes","volume":"35","author":"Long","year":"2014","journal-title":"Tumor. Biol."},{"key":"ref_106","unstructured":"(2020, January 10). Clinical Trial Identification Number, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02980029."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1002\/cam4.711","article-title":"Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway","volume":"5","author":"Wang","year":"2016","journal-title":"Cancer Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1158\/0008-5472.CAN-11-4057","article-title":"Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer","volume":"72","author":"Zaytseva","year":"2012","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/jnci\/djr542","article-title":"Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses\u2019 health study","volume":"104","author":"Kuchiba","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00432-015-2000-8","article-title":"Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway","volume":"142","author":"Chang","year":"2016","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1093\/jnci\/86.15.1122","article-title":"Dose de-escalation chemoprevention trial of \u03b1-difluoromethylornithine in patients with colon polyps","volume":"86","author":"Meyskens","year":"1994","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1940-6207.CAPR-08-0042","article-title":"Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: A randomized placebo-controlled, double-blind trial","volume":"1","author":"Meyskens","year":"2008","journal-title":"Cancer Prev. Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"McCann, P.P., Pegg, A.E., and Sjoerdsma, A. (1987). Polyamine inhibition in vivo and in organ growth and repair. Inhibition of Polyamine Metabolism, Academic Press.","DOI":"10.1016\/B978-0-12-481835-4.50004-1"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"37046","DOI":"10.1038\/srep37046","article-title":"Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer","volume":"6","author":"Janakiram","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_115","first-page":"4528","article-title":"Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, alpha-difluoromethylornithine, 16 alpha-fluoro-5-androsten-17-one, and ellagic acid individually and in combination","volume":"51","author":"Rao","year":"1991","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1021\/jf204128z","article-title":"Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats","volume":"60","author":"Kumar","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1002\/cam4.2151","article-title":"Statin uses and mortality in colorectal cancer patients: An updated systematic review and meta-analysis","volume":"8","author":"Li","year":"2019","journal-title":"Cancer Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s00464-017-5841-1","article-title":"Simvastatin enhances radiation sensitivity of colorectal cancer cells","volume":"32","author":"Karagkounis","year":"2018","journal-title":"Surg. Endosc."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1158\/1078-0432.CCR-17-2859","article-title":"Prevention of Colitis and Colitis-Associated Colorectal Cancer by a Novel Polypharmacological Histone Deacetylase Inhibitor","volume":"24","author":"Wei","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1158\/1940-6207.CAPR-11-0222","article-title":"Combination of atorvastatin with sulindac or naproxen profoundly inhibits colonic adenocarcinomas by suppressing the p65\/\u03b2-catenin\/cyclin D1 signaling pathway in rats","volume":"4","author":"Suh","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1158\/0008-5472.CAN-05-4619","article-title":"Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice","volume":"66","author":"Swamy","year":"2006","journal-title":"Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1158\/1940-6207.CAPR-10-0007","article-title":"Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer","volume":"3","author":"Lipkin","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nrgastro.2016.56","article-title":"Chemoprevention of hereditary colon cancers: Time for new strategies","volume":"13","author":"Ricciardiello","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_124","unstructured":"(2020, January 10). Clinical Trial Identification Number, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02301286."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00428-009-0777-z","article-title":"Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients","volume":"454","author":"Seo","year":"2009","journal-title":"Virchows Arch."},{"key":"ref_126","first-page":"293","article-title":"Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis","volume":"60","author":"Reddy","year":"2000","journal-title":"Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1136\/gutjnl-2014-308260","article-title":"Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: A meta-analysis","volume":"64","author":"Li","year":"2015","journal-title":"Gut"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4103\/1477-3163.78279","article-title":"The AOM\/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies","volume":"10","author":"Massi","year":"2011","journal-title":"J. Carcinog."},{"key":"ref_129","first-page":"80","article-title":"More than two decades of Apc modeling in rodents","volume":"1836","author":"Zeineldin","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"11859","DOI":"10.1073\/pnas.1614057113","article-title":"Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research","volume":"113","author":"Tetteh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"E488","DOI":"10.1002\/ijc.29232","article-title":"Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc","volume":"136","author":"Femia","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00394-019-01948-z","article-title":"A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344\/NTac-Apcam1137)","volume":"59","author":"Navarra","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"450","DOI":"10.5732\/cjc.011.10041","article-title":"Mouse models of colorectal cancer","volume":"30","author":"Tong","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1053\/j.gastro.2008.12.049","article-title":"Mouse models of colon cancer","volume":"136","author":"Taketo","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.molonc.2013.02.006","article-title":"What are the best routes to effectively model human colorectal cancer?","volume":"7","author":"Young","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ame2.12102","article-title":"The role of mouse models in colorectal cancer research-The need and the importance of the orthotopic models","volume":"3","author":"Oliveira","year":"2020","journal-title":"Anim. Models Exp. Med."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Inoue, A., Deem, A.K., Kopetz, S., Heffernan, T.P., Draetta, G.F., and Carugo, A. (2019). Current and Future Horizons of Patient-Derived Xenograft Models in Colorectal Cancer Translational Research. Cancers, 11.","DOI":"10.3390\/cancers11091321"},{"key":"ref_138","first-page":"S1","article-title":"LFA-9, a Selective Inhibitor of Microsomal Prostaglandin Synthase-1 and 5-Lipoxygenase","volume":"34","author":"Yarla","year":"2020","journal-title":"Prev. Inflamm. Oncol. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9609\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:11Z","timestamp":1760179571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":138,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249609"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249609","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]}}}