{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:29Z","timestamp":1790661929011,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Prostate cancer is the most commonly diagnosed non-cutaneous cancer in males and the second leading cause of male cancer death in the United States. Androgen deprivation therapy to block androgen receptor (AR) signaling is part of the standard of care. However, approximately 30%\u201340% of patients experience biochemical recurrence (BCR) after primary therapy and progress to a more lethal form of castration-resistant prostate cancer for which there currently is no curative therapy. This study focused on patients at risk of progressing to BCR with the aim of identifying novel combinatorial targets that can be used with AR inhibition to provide greater therapeutic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Personalized Boolean network models were developed using The Cancer Genome Atlas and in-house data to integrate mutations, copy number alterations, and RNA-seq data. Asynchronous stochastic network simulations in MaBoSS (Markovian Boolean Stochastic Simulator) were used to identify potential drug targets in combination with AR inhibition, which were cross-checked using a machine learning algorithm and tested with a cytotoxicity assay across 4 prostate cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In silico<\/jats:italic>\n                      predictions and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments showed that target-specific co-inhibition of E2F1 or Cyclin B with an AR antagonist enhances enzalutamide-associated growth inhibition in all 4 prostate cancer cell lines. Pharmacodynamic modeling suggested that the drug combinations were synergistic with all interaction parameters estimated to be less than 1 (range = 0.156-0.834).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Dynamic profiling of personalized Boolean networks in treatment-na\u00efve prostate cancer subjects with and without BCR identified potential drug targets in combination with AR antagonists. Future xenograft studies are needed to confirm\n                      <jats:italic>in vitro<\/jats:italic>\n                      results, and exposure-response modeling could provide guidance for feasibility assessment and clinical trial design.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1869953","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:04Z","timestamp":1790661004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized Boolean network dynamic profiling and machine learning approaches to identify combinatorial treatments for prostate cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Se Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Pharmacokinetics-Pharmacodynamics & Systems Pharmacology, Department of Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Salib","sequence":"additional","affiliation":[{"name":"Division of Pharmacokinetics-Pharmacodynamics & Systems Pharmacology, Department of Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center","place":["Buffalo, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Woloszynska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center","place":["Buffalo, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Mager","sequence":"additional","affiliation":[{"name":"Division of Pharmacokinetics-Pharmacodynamics & Systems Pharmacology, Department of Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, NY, United States"]},{"name":"Enhanced Pharmacodynamics, LLC","place":["Buffalo, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","unstructured":""},{"key":"B2","volume-title":"Cancer Facts and Figures","year":""},{"key":"B3","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.3389\/fphys.2018.01965","article-title":"Personalization of logical models with multi-omics data allows clinical stratification of patients","volume":"9","author":"Beal","year":"2018","journal-title":"Front. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s10928-017-9567-4","article-title":"Boolean network modeling in systems pharmacology","volume":"45","author":"Bloomingdale","year":"2018","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/a:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/sj.cdd.4401130","article-title":"Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe","volume":"9","author":"Castedo","year":"2002","journal-title":"Cell Death Differ."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1002\/jps.3000","article-title":"Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation","volume":"91","author":"Chakraborty","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1106175","DOI":"10.3389\/fendo.2022.1106175","article-title":"CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1124\/jpet.115.224766","article-title":"Logic-based and cellular pharmacodynamic modeling of bortezomib responses in U266 human myeloma cells","volume":"354","author":"Chudasama","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1126\/science.1160165","article-title":"Dynamic proteomics of individual cancer cells in response to a drug","volume":"322","author":"Cohen","year":"2008","journal-title":"Science"},{"key":"B11","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1001\/jama.280.11.969","article-title":"Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer","volume":"280","author":"D'Amico","year":"1998","journal-title":"JAMA"},{"key":"B12","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/nrd2089","article-title":"Strategies for optimizing combinations of molecularly targeted anticancer agents","volume":"5","author":"Dancey","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"B13","doi-asserted-by":"publisher","first-page":"8643","DOI":"10.1158\/0008-5472.can-07-6611","article-title":"A history of cancer chemotherapy","volume":"68","author":"Devita","year":"2008","journal-title":"Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/sj.cgt.7700416","article-title":"Inhibition of LNCaP prostate tumor growth in vivo by an antisense oligonucleotide directed against the human androgen receptor","volume":"9","author":"Eder","year":"2002","journal-title":"Cancer Gene Ther."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1158\/0008-5472.CAN-17-0078","article-title":"Drug resistance mechanisms in colorectal cancer dissected with cell type-specific dynamic logic models","volume":"77","author":"Eduati","year":"2017","journal-title":"Cancer Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e9690","DOI":"10.15252\/msb.20188664","article-title":"Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies","volume":"16","author":"Eduati","year":"2020","journal-title":"Mol. Syst. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s10552-007-9083-8","article-title":"Quantifying the role of PSA screening in the US prostate cancer mortality decline","volume":"19","author":"Etzioni","year":"2008","journal-title":"Cancer Causes Control"},{"key":"B18","doi-asserted-by":"publisher","first-page":"ra130","DOI":"10.1126\/scisignal.aab0990","article-title":"Signaling pathway models as biomarkers: patient-specific simulations of JNK activity predict the survival of neuroblastoma patients","volume":"8","author":"Fey","year":"2015","journal-title":"Sci. Signal"},{"key":"B19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1464-410X.2007.07487.x","article-title":"Management of localized prostate cancer in senior adults: the crucial role of comorbidity","volume":"101","author":"Fitzpatrick","year":"2008","journal-title":"BJU Int."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1004426","DOI":"10.1371\/journal.pcbi.1004426","article-title":"Discovery of drug synergies in gastric cancer cells predicted by logical modeling","volume":"11","author":"Flobak","year":"2015","journal-title":"PLoS Comput. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1001\/jama.294.4.433","article-title":"Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy","volume":"294","author":"Freedland","year":"2005","journal-title":"JAMA"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e69008","DOI":"10.1371\/journal.pone.0069008","article-title":"Boolean network model for cancer pathways: predicting carcinogenesis and targeted therapy outcomes","volume":"8","author":"Fumia","year":"2013","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41585-020-00400-w","article-title":"Genomic and phenotypic heterogeneity in prostate cancer","volume":"18","author":"Haffner","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"831329","DOI":"10.3389\/fcell.2022.831329","article-title":"Differential expression of E2F transcription factors and their functional and prognostic roles in human prostate cancer","volume":"10","author":"Han","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s10928-014-9352-6","article-title":"Ubiquity: a framework for physiological\/mechanism-based pharmacokinetic\/pharmacodynamic model development and deployment","volume":"41","author":"Harrold","year":"2014","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"B26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1517\/17460441.2016.1135126","article-title":"Providing data science support for systems pharmacology and its implications to drug discovery","volume":"11","author":"Hart","year":"2016","journal-title":"Expert Opin. Drug Discov."},{"key":"B27","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1210\/er.2002-0032","article-title":"Androgen receptor in prostate cancer","volume":"25","author":"Heinlein","year":"2004","journal-title":"Endocr. Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0002-9440(10)63112-4","article-title":"Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance","volume":"164","author":"Holzbeierlein","year":"2004","journal-title":"Am. J. Pathol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"17280","DOI":"10.1038\/srep17280","article-title":"Integrated network model provides new insights into castration-resistant prostate cancer","volume":"5","author":"Hu","year":"2015","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"128701","DOI":"10.1103\/PhysRevLett.94.128701","article-title":"Cell fates as high-dimensional attractor states of a complex gene regulatory network","volume":"94","author":"Huang","year":"2005","journal-title":"Phys. Rev. Lett."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030690","article-title":"Comparative molecular analysis of cancer behavior cultured in vitro,in vivo, and Ex Vivo","volume":"12","author":"Hum","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"103944","DOI":"10.1016\/j.isci.2022.103944","article-title":"A text-based computational framework for patient -specific modeling for classification of cancers","volume":"25","author":"Imoto","year":"2022","journal-title":"iScience"},{"key":"B33","doi-asserted-by":"publisher","first-page":"d447","DOI":"10.2741\/a291","article-title":"Role of E2F in cell cycle control and cancer","volume":"3","author":"Johnson","year":"1998","journal-title":"Front. Biosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/0022-5193(69)90015-0","article-title":"Metabolic stability and epigenesis in randomly constructed genetic nets","volume":"22","author":"Kauffman","year":"1969","journal-title":"J. Theor. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"ra68","DOI":"10.1126\/scisignal.2004008","article-title":"Computational modeling of ERBB2-amplified breast cancer identifies combined ErbB2\/3 blockade as superior to the combination of MEK and AKT inhibitors","volume":"6","author":"Kirouac","year":"2013","journal-title":"Sci. Signal"},{"key":"B36","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.csbj.2016.09.002","article-title":"The promises of quantitative systems pharmacology modelling for drug development","volume":"14","author":"Knight-Schrijver","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B37","volume-title":"Tidymodels: A Collection of Packages for Modeling and Machine Learning Using Tidyverse Principles","author":"Kuhn","year":"2020"},{"key":"B38","doi-asserted-by":"publisher","first-page":"14739","DOI":"10.1038\/srep14739","article-title":"Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets","volume":"5","author":"Lu","year":"2015","journal-title":"Sci. Rep."},{"key":"B39","article-title":"Systems pharmacology and pharmacodynamics: an introduction","author":"Mager","year":"2016","journal-title":"AAPS Adv. Pharm. Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nrc1295","article-title":"Dynamics of cancer progression","volume":"4","author":"Michor","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1097\/01.ju.0000155535.25971.de","article-title":"Ability of 2 pretreatment risk assessment methods to predict prostate cancer recurrence after radical prostatectomy: data from CaPSURE","volume":"173","author":"Mitchell","year":"2005","journal-title":"J. Urol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e72626","DOI":"10.7554\/eLife.72626","article-title":"Patient-specific Boolean models of signalling networks guide personalised treatments","volume":"11","author":"Montagud","year":"2022","journal-title":"Elife"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1002\/cpt.1434","article-title":"Pharmacodynamic drug-drug interactions","volume":"105","author":"Niu","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.semcancer.2011.07.002","article-title":"Progress in treatment and risk stratification of neuroblastoma: impact on future clinical and basic research","volume":"21","author":"Ora","year":"2011","journal-title":"Semin. Cancer Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1016\/j.cell.2017.11.009","article-title":"Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy","volume":"171","author":"Palmer","year":"2017","journal-title":"Cell"},{"key":"B46","volume-title":"Quantitative and Systems Pharmacology in the Post-genomic Era: New Approaches to Discovering Drugs and Understanding Therapeutic Mechanisms.","author":"Peter Sorger","year":"2011"},{"key":"B47","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1023\/a:1014457510073","article-title":"Lack of in vitro-in vivo correlation of a novel investigational anticancer agent, SH 30","volume":"20","author":"Poondru","year":"2002","journal-title":"Invest New Drugs"},{"key":"B48","doi-asserted-by":"publisher","first-page":"300","DOI":"10.5173\/ceju.2020.0067R","article-title":"Modern biomarkers in prostate cancer diagnosis","volume":"73","author":"Porzycki","year":"2020","journal-title":"Cent. Eur. J. Urol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"127rv3","DOI":"10.1126\/scitranslmed.3003180","article-title":"Beyond PSA: the next generation of prostate cancer biomarkers","volume":"4","author":"Prensner","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.cell.2013.02.005","article-title":"Encoding and decoding cellular information through signaling dynamics","volume":"152","author":"Purvis","year":"2013","journal-title":"Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13073-024-01323-6","article-title":"Race-specific coregulatory and transcriptomic profiles associated with DNA methylation and androgen receptor in prostate cancer","volume":"16","author":"Ramakrishnan","year":"2024","journal-title":"Genome Med."},{"key":"B52","first-page":"9","volume":"7","author":"Rebello","year":"2021","journal-title":"Prostate Cancer. Nat. Rev. Dis. Prim."},{"key":"B53","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41419-018-0566-1","article-title":"E2F1 inhibition mediates cell death of metastatic melanoma","volume":"9","author":"Rouaud","year":"2018","journal-title":"Cell Death Dis."},{"key":"B54","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.jtbi.2010.07.022","article-title":"Attractor analysis of asynchronous Boolean models of signal transduction networks","volume":"266","author":"Saadatpour","year":"2010","journal-title":"J. Theor. Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e1002267","DOI":"10.1371\/journal.pcbi.1002267","article-title":"Dynamical and structural analysis of a T cell survival network identifies novel candidate therapeutic targets for large granular lymphocyte leukemia","volume":"7","author":"Saadatpour","year":"2011","journal-title":"PLoS Comput. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e163","DOI":"10.1371\/journal.pcbi.0030163","article-title":"A logical model provides insights into T cell receptor signaling","volume":"3","author":"Saez-Rodriguez","year":"2007","journal-title":"PLoS Comput. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5400","DOI":"10.1158\/0008-5472.CAN-10-4453","article-title":"Comparing signaling networks between normal and transformed hepatocytes using discrete logical models","volume":"71","author":"Saez-Rodriguez","year":"2011","journal-title":"Cancer Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1056\/nejmoa1910549","article-title":"Pembrolizumab for early triple-negative breast cancer","volume":"382","author":"Schmid","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/s41391-023-00712-z","article-title":"Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification","volume":"27","author":"Shore","year":"2024","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1083\/jcb.201612010","article-title":"Why proteomics is not the new genomics and the future of mass spectrometry in cell biology","volume":"216","author":"Sidoli","year":"2017","journal-title":"J. Cell Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/1752-0509-6-116","article-title":"Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm","volume":"6","author":"Stoll","year":"2012","journal-title":"BMC Syst. Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1471-2105-8-25","article-title":"Bias in random forest variable importance measures: illustrations, sources and a solution","volume":"8","author":"Strobl","year":"2007","journal-title":"BMC Bioinforma."},{"key":"B63","doi-asserted-by":"publisher","first-page":"119264","DOI":"10.1016\/j.biomaterials.2019.119264","article-title":"Synergistic triple-combination therapy with hyaluronic acid-shelled PPy\/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer","volume":"217","author":"Sun","year":"2019","journal-title":"Biomaterials"},{"key":"B64","year":"2006"},{"key":"B65","unstructured":"Duration of siRNA-induced silencing\n          \n          \n          2026"},{"key":"B66","doi-asserted-by":"publisher","first-page":"055001","DOI":"10.1088\/1478-3975\/9\/5\/055001","article-title":"Boolean modeling in systems biology: an overview of methodology and applications","volume":"9","author":"Wang","year":"2012","journal-title":"Phys. Biol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"5095","DOI":"10.21037\/tcr-21-1532","article-title":"Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation","volume":"10","author":"Wang","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1869953\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:07Z","timestamp":1790661007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1869953\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":68,"alternative-id":["10.3389\/fphar.2026.1869953"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1869953","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"1869953"}}