{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:29:50Z","timestamp":1785868190630,"version":"3.56.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine, University of Saskatchewan","award":["CoMRAD, 417742"],"award-info":[{"award-number":["CoMRAD, 417742"]}]},{"name":"Cancer Foundation of Saskatchewan","award":["Saskatchewan Cancer Agency Operating grant (425535)"],"award-info":[{"award-number":["Saskatchewan Cancer Agency Operating grant (425535)"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec120\">\n                    <jats:title\/>\n                    <jats:p>\n                      Lung squamous cell carcinoma (LUSC) is a difficult cancer to treat, with few targeted therapies to improve its poor prognosis. The goal of this study was to use a drug repurposing strategy to evaluate and compare drug sensitivities using 2D adherent and 3D spheroid models of NCI-H2170 LUSC cells. Both 2D adherent and 3D spheroid models were used to grow NCI-H2170 lung squamous cell carcinoma cells and evaluate their sensitivity to a large library of food and drug administration (FDA)-approved drugs, including many not typically used as anti-cancer agents. Cell death was assessed in the 2D adherent models, and for the top drugs half maximal effective concentration (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) values were determined. For the 3D spheroid models, drugs reducing spheroid size after 4 days of treatment were identified. There were 263 drugs that reduced the cell viability to &lt;20% when cells were grown in 2D in 10 \u00b5M drug. When grown in 3D the cells were generally more drug resistant, with 87 drugs capable of reducing spheroid volume when grown over 4 days in 10 \u00b5M drug. Interestingly, 60 drugs proved effective in both model systems including many drugs that typically associated with anti-cancer properties. Of these 60, four were further found to have selective effects towards metastatic NCI-H2170 cells as compared to a much less metastatic matched cell line expressing the metastasis suppressor CREB3L1, in both 2D and 3D model systems. These included the hypoxia-inducible factor 1-alpha (HIF-1\u03b1 inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec001\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that the HIF-1\u03b1 inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione) may be effective for metastatic LUSCs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355486","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:30:48Z","timestamp":1785864648000},"page":"e0355486","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["2-methoxyestradiol is effective in 2D and 3D models of NCI-H2170 lung squamous cell carcinoma cells"],"prefix":"10.1371","volume":"21","author":[{"given":"Paul","family":"Mellor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Kendall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-2540","authenticated-orcid":true,"given":"Deborah H.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"6","key":"pone.0355486.ref001","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"F Bray","year":"2018","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"4","key":"pone.0355486.ref002","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1378\/chest.08-2484","article-title":"Histologic considerations for individualized systemic therapy approaches for the management of non-small cell lung cancer","volume":"136","author":"H West","year":"2009","journal-title":"Chest"},{"key":"pone.0355486.ref003","year":"2017"},{"issue":"1","key":"pone.0355486.ref004","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1158\/2159-8274.CD-11-0005","article-title":"Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer","volume":"1","author":"PS Hammerman","year":"2011","journal-title":"Cancer Discov"},{"issue":"7417","key":"pone.0355486.ref005","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature11404","article-title":"Comprehensive genomic characterization of squamous cell lung cancers","volume":"489","author":"Cancer Genome Atlas Research Network","year":"2012","journal-title":"Nature"},{"issue":"4","key":"pone.0355486.ref006","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2217\/lmt.12.40","article-title":"Targeted therapy for squamous cell lung cancer","volume":"1","author":"RG Liao","year":"2012","journal-title":"Lung Cancer Manag"},{"issue":"8","key":"pone.0355486.ref007","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.mayocp.2019.01.013","article-title":"Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment","volume":"94","author":"N Duma","year":"2019","journal-title":"Mayo Clin Proc"},{"issue":"1","key":"pone.0355486.ref008","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13058-016-0672-x","article-title":"Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers","volume":"18","author":"AK Ward","year":"2016","journal-title":"Breast Cancer Res"},{"issue":"24","key":"pone.0355486.ref009","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1128\/MCB.00959-13","article-title":"CREB3L1 is a metastasis suppressor that represses expression of genes regulating metastasis, invasion, and angiogenesis","volume":"33","author":"P Mellor","year":"2013","journal-title":"Mol Cell Biol"},{"issue":"12","key":"pone.0355486.ref010","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.4161\/15592294.2014.988052","article-title":"OASIS\/CREB3L1 is epigenetically silenced in human bladder cancer facilitating tumor cell spreading and migration in vitro","volume":"9","author":"M Rose","year":"2014","journal-title":"Epigenetics"},{"key":"pone.0355486.ref011","doi-asserted-by":"crossref","first-page":"4817924","DOI":"10.1155\/2024\/4817924","article-title":"KIF26B and CREB3L1 Derived from Immunoscore Could Inhibit the Progression of Ovarian Cancer","volume":"2024","author":"S Cong","year":"2024","journal-title":"J Immunol Res"},{"issue":"6","key":"pone.0355486.ref012","doi-asserted-by":"crossref","first-page":"167845","DOI":"10.1016\/j.bbadis.2025.167845","article-title":"Expression of CREB3L1 blocks key cancer pathways and suppresses metastasis of lung squamous cell carcinoma cells","volume":"1871","author":"P Mellor","year":"2025","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"7","key":"pone.0355486.ref013","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"D Ron","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"2","key":"pone.0355486.ref014","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/ncb1213","article-title":"OASIS, a CREB\/ATF-family member, modulates UPR signalling in astrocytes","volume":"7","author":"S Kondo","year":"2005","journal-title":"Nat Cell Biol"},{"issue":"10","key":"pone.0355486.ref015","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/ncb1963","article-title":"Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation","volume":"11","author":"T Murakami","year":"2009","journal-title":"Nat Cell Biol"},{"issue":"5852","key":"pone.0355486.ref016","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1126\/science.1146361","article-title":"IRE1 signaling affects cell fate during the unfolded protein response","volume":"318","author":"JH Lin","year":"2007","journal-title":"Science"},{"issue":"9","key":"pone.0355486.ref017","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/sj.embor.7400779","article-title":"Mediators of endoplasmic reticulum stress-induced apoptosis","volume":"7","author":"E Szegezdi","year":"2006","journal-title":"EMBO Rep"},{"key":"pone.0355486.ref018","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40425-016-0203-4","article-title":"Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer","volume":"5","author":"JR Cubillos-Ruiz","year":"2017","journal-title":"J Immunother Cancer"},{"issue":"1","key":"pone.0355486.ref019","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0169-328X(99)00102-3","article-title":"Identification of a novel gene, OASIS, which encodes for a putative CREB\/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue","volume":"69","author":"Y Honma","year":"1999","journal-title":"Brain Res Mol Brain Res"},{"issue":"7","key":"pone.0355486.ref020","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1083\/jcb.201110131","article-title":"The impact of the unfolded protein response on human disease","volume":"197","author":"S Wang","year":"2012","journal-title":"J Cell Biol"},{"issue":"3","key":"pone.0355486.ref021","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ncb0311-184","article-title":"Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress","volume":"13","author":"I Tabas","year":"2011","journal-title":"Nat Cell Biol"},{"issue":"7","key":"pone.0355486.ref022","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00258.2014","article-title":"Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 1. An overview","volume":"307","author":"E Dufey","year":"2014","journal-title":"Am J Physiol Cell Physiol"},{"issue":"5","key":"pone.0355486.ref023","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S1097-2765(00)00108-8","article-title":"Regulated translation initiation controls stress-induced gene expression in mammalian cells","volume":"6","author":"HP Harding","year":"2000","journal-title":"Mol Cell"},{"issue":"25","key":"pone.0355486.ref024","doi-asserted-by":"crossref","first-page":"25935","DOI":"10.1074\/jbc.R400008200","article-title":"Signaling the unfolded protein response from the endoplasmic reticulum","volume":"279","author":"K Zhang","year":"2004","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0355486.ref025","doi-asserted-by":"crossref","first-page":"15663","DOI":"10.1038\/s41598-022-19621-7","article-title":"Homoharringtonine demonstrates a cytotoxic effect against triple-negative breast cancer cell lines and acts synergistically with paclitaxel","volume":"12","author":"R Plett","year":"2022","journal-title":"Sci Rep"},{"issue":"7","key":"pone.0355486.ref026","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1177\/1087057107306839","article-title":"A reliable tool to determine cell viability in complex 3-d culture: the acid phosphatase assay","volume":"12","author":"J Friedrich","year":"2007","journal-title":"J Biomol Screen"},{"issue":"1","key":"pone.0355486.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2613.1998.00051.x","article-title":"Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology","volume":"79","author":"LA Kunz-Schughart","year":"1998","journal-title":"Int J Exp Pathol"},{"issue":"4","key":"pone.0355486.ref028","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth1015","article-title":"Three-dimensional culture models of normal and malignant breast epithelial cells","volume":"4","author":"GY Lee","year":"2007","journal-title":"Nat Methods"},{"issue":"5","key":"pone.0355486.ref029","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.semcancer.2005.05.001","article-title":"Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation","volume":"15","author":"CM Nelson","year":"2005","journal-title":"Semin Cancer Biol"},{"issue":"12","key":"pone.0355486.ref030","first-page":"4155","article-title":"Overexpressed HER2 in NSCLC is a possible therapeutic target of EGFR inhibitors","volume":"31","author":"N Ise","year":"2011","journal-title":"Anticancer Res"},{"issue":"3","key":"pone.0355486.ref031","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.bbrc.2020.08.075","article-title":"Differences in drug sensitivity between two-dimensional and three-dimensional culture systems in triple-negative breast cancer cell lines","volume":"533","author":"M Muguruma","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0355486.ref032","doi-asserted-by":"crossref","first-page":"18380","DOI":"10.1038\/s41598-023-45144-w","article-title":"Comparative analysis between 2D and 3D colorectal cancer culture models for insights into cellular morphological and transcriptomic variations","volume":"13","author":"ZN Abbas","year":"2023","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0355486.ref033","article-title":"Cetylpyridinium Chloride: Mechanism of Action, Antimicrobial Efficacy in Biofilms, and Potential Risks of Resistance","volume":"64","author":"X Mao","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0355486.ref034","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mito.2019.09.009","article-title":"Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer","volume":"50","author":"SA Allen","year":"2020","journal-title":"Mitochondrion"},{"key":"pone.0355486.ref035","first-page":"22808000221092157","article-title":"Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way","volume":"20","author":"CM Garc\u00eda-Cuellar","year":"2022","journal-title":"J Appl Biomater Funct Mater"},{"issue":"8","key":"pone.0355486.ref036","doi-asserted-by":"crossref","first-page":"110598","DOI":"10.1016\/j.isci.2024.110598","article-title":"Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway","volume":"27","author":"H Tang","year":"2024","journal-title":"iScience"},{"issue":"9","key":"pone.0355486.ref037","article-title":"Cetylpyridinium chloride inhibits hepatocellular carcinoma growth and metastasis through regulating epithelial-mesenchymal transition and apoptosis","volume":"19","author":"K Cai","year":"2024","journal-title":"PLoS One"},{"issue":"1","key":"pone.0355486.ref038","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/CMR.12.1.147","article-title":"Antiseptics and disinfectants: activity, action, and resistance","volume":"12","author":"G McDonnell","year":"1999","journal-title":"Clin Microbiol Rev"},{"issue":"12","key":"pone.0355486.ref039","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.21873\/anticanres.17369","article-title":"Chlorhexidine Dihydrochloride Shows Anti-tumor Effects in Desmoid Tumors and Colorectal Cancer","volume":"44","author":"H Shin","year":"2024","journal-title":"Anticancer Research"},{"issue":"3","key":"pone.0355486.ref040","first-page":"201","article-title":"Anticancer activity of chlorhexidine and cranberry extract: an in-vitro study","volume":"12","author":"MR Khairnar","year":"2018","journal-title":"J Exp Ther Oncol"},{"issue":"8","key":"pone.0355486.ref041","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1016\/j.molonc.2015.05.005","article-title":"Anticancer activity of pyrithione zinc in oral cancer cells identified in small molecule screens and xenograft model: Implications for oral cancer therapy","volume":"9","author":"G Srivastava","year":"2015","journal-title":"Mol Oncol"},{"issue":"8","key":"pone.0355486.ref042","doi-asserted-by":"crossref","first-page":"13942","DOI":"10.18632\/oncotarget.14572","article-title":"Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases","volume":"8","author":"C Zhao","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0355486.ref043","doi-asserted-by":"crossref","first-page":"23060","DOI":"10.1038\/s41598-023-49740-8","article-title":"Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal\/astrocytic co-cultured cells via oxidative stress","volume":"13","author":"H-N Oh","year":"2023","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0355486.ref044","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.bbamcr.2008.09.010","article-title":"Intracellular zinc increase inhibits p53(-\/-) pancreatic adenocarcinoma cell growth by ROS\/AIF-mediated apoptosis","volume":"1793","author":"M Donadelli","year":"2009","journal-title":"Biochim Biophys Acta"},{"issue":"20","key":"pone.0355486.ref045","doi-asserted-by":"crossref","DOI":"10.1503\/cmaj.161455","article-title":"Sodium-glucose cotransporter 2 inhibitors for treating diabetes mellitus","volume":"189","author":"N Goldberg","year":"2017","journal-title":"CMAJ"},{"issue":"11","key":"pone.0355486.ref046","doi-asserted-by":"crossref","first-page":"108218","DOI":"10.1016\/j.isci.2023.108218","article-title":"Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer","volume":"26","author":"X Yang","year":"2023","journal-title":"iScience"},{"issue":"1","key":"pone.0355486.ref047","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00775-010-0736-9","article-title":"Zinc is decreased in prostate cancer: an established relationship of prostate cancer!","volume":"16","author":"LC Costello","year":"2011","journal-title":"J Biol Inorg Chem"},{"issue":"8","key":"pone.0355486.ref048","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3390\/nu4080875","article-title":"Cellular mechanisms of zinc dysregulation: a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer","volume":"4","author":"S Alam","year":"2012","journal-title":"Nutrients"},{"issue":"5","key":"pone.0355486.ref049","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s10534-011-9441-6","article-title":"Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis","volume":"24","author":"SD Lamore","year":"2011","journal-title":"Biometals"},{"key":"pone.0355486.ref050","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1023\/A:1026543018478","article-title":"2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate","volume":"19","author":"VS Pribluda","year":"2000","journal-title":"Cancer Metastasis Rev"},{"issue":"2","key":"pone.0355486.ref051","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1592\/phco.23.2.165.32088","article-title":"2-Methoxyestradiol, a promising anticancer agent","volume":"23","author":"NJ Lakhani","year":"2003","journal-title":"Pharmacotherapy"},{"issue":"4","key":"pone.0355486.ref052","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S1535-6108(03)00077-1","article-title":"2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF","volume":"3","author":"NJ Mabjeesh","year":"2003","journal-title":"Cancer Cell"},{"issue":"9","key":"pone.0355486.ref053","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1073\/pnas.91.9.3964","article-title":"2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site","volume":"91","author":"RJ D\u2019Amato","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pone.0355486.ref054","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00294-020-01093-9","article-title":"Roles of the PH, coiled-coil and SAM domains of the yeast polarity protein Boi2 in polarity-site localization and function in polarized growth","volume":"66","author":"Z-W Jia","year":"2020","journal-title":"Curr Genet"},{"issue":"5","key":"pone.0355486.ref055","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1021\/mp1001119","article-title":"Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism","volume":"7","author":"K Sugano","year":"2010","journal-title":"Mol Pharm"},{"issue":"6","key":"pone.0355486.ref056","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s13197-024-05927-z","article-title":"Coffee leaf valorisation into functional wheat flour rusk: their nutritional, physicochemical, and sensory properties","volume":"61","author":"SS Patil","year":"2024","journal-title":"J Food Sci Technol"},{"issue":"7","key":"pone.0355486.ref057","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s004320000233","article-title":"The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors","volume":"127","author":"G Schumacher","year":"2001","journal-title":"J Cancer Res Clin Oncol"},{"issue":"1","key":"pone.0355486.ref058","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2021.e05948","article-title":"Drug combination and repurposing for cancer therapy: the example of breast cancer","volume":"7","author":"AS Correia","year":"2021","journal-title":"Heliyon"},{"issue":"15","key":"pone.0355486.ref059","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.3390\/cancers14153692","article-title":"Advanced Cellular Models for Preclinical Drug Testing: From 2D Cultures to Organ-on-a-Chip Technology","volume":"14","author":"V Foglizzo","year":"2022","journal-title":"Cancers (Basel)"},{"key":"pone.0355486.ref060","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-1-0716-4901-5_10","article-title":"3D Spheroid Model: A Methodological Approach for Advancing Cancer and Immunology Research","volume":"2983","author":"DC Rouse","year":"2026","journal-title":"Methods in molecular biology"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:30:58Z","timestamp":1785864658000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355486"}},"subtitle":[],"editor":[{"given":"Alireza","family":"Shoari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355486","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}