{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:26:59Z","timestamp":1787308019063,"version":"build-2736575974"},"reference-count":84,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Vascularized tumor organoid and tumor-on-chip models are increasingly used to examine treatment response, yet a weak therapeutic effect does not by itself identify the failed transport or biological step. Reduced efficacy may result from inadequate delivery, altered endothelial transport or signaling, stromal protection, impaired immune access or function, tumor-intrinsic resistance, or several processes acting together. A structured literature search and narrative synthesis were combined with a focused qualitative appraisal of 25 eligible primary studies to determine what evidence is needed to distinguish these explanations. Twenty-one studies included a relevant comparator, a mechanism-directed perturbation, and a functional readout; four directly tested a principal competing explanation, and three included rescue or reversal. Most studies therefore supported a contributory mechanism under the tested conditions rather than an exclusive causal attribution, leaving transport, stromal, immune, and tumor-intrinsic routes incompletely separated. The synthesis defines five candidate failed-step classes and specifies the comparisons, local-exposure or step-resolved measurements, perturbations, orthogonal readouts, and alternative tests needed for each. Mechanistic attribution is most secure when the proposed bottleneck is measured directly, manipulated experimentally, and distinguished from credible alternatives. Clinical application will additionally require context-of-use-specific evidence of analytical reproducibility, reference treatments, prespecified acceptance criteria, and association with clinically relevant outcomes.<\/jats:p>","DOI":"10.3390\/bioengineering13080947","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:31:59Z","timestamp":1787304719000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Vascularization in Tumor Organoid and Tumor-on-Chip Models: Evidence Requirements for Attributing Therapy-Resistance Mechanisms"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2388-1587","authenticated-orcid":false,"given":"Yafang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongjiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: New dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1200\/JCO.2012.46.3653","article-title":"Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers","volume":"31","author":"Jain","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15101","DOI":"10.1073\/pnas.1213353109","article-title":"Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors","volume":"109","author":"Stylianopoulos","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"0004","DOI":"10.1038\/s41551-016-0004","article-title":"Solid stress and elastic energy as measures of tumour mechanopathology","volume":"1","author":"Nia","year":"2017","journal-title":"Nat. Biomed. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrclinonc.2018.29","article-title":"Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges","volume":"15","author":"Fukumura","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cell.2015.03.053","article-title":"Prospective derivation of a living organoid biobank of colorectal cancer patients","volume":"161","author":"Francies","year":"2015","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cell.2017.11.010","article-title":"A living biobank of breast cancer organoids captures disease heterogeneity","volume":"172","author":"Sachs","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.aao2774","article-title":"Patient-derived organoids model treatment response of metastatic gastrointestinal cancers","volume":"359","author":"Vlachogiannis","year":"2018","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1126\/science.aaw6985","article-title":"Cancer modeling meets human organoid technology","volume":"364","author":"Tuveson","year":"2019","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2303161","DOI":"10.1002\/adhm.202303161","article-title":"Patient-derived microphysiological systems for precision medicine","volume":"13","author":"Ko","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s43586-022-00118-6","article-title":"A guide to the organ-on-a-chip","volume":"2","author":"Leung","year":"2022","journal-title":"Nat. Rev. Methods Prim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41576-022-00466-9","article-title":"Human organs-on-chips for disease modelling, drug development and personalized medicine","volume":"23","author":"Ingber","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nbt.2989","article-title":"Microfluidic organs-on-chips","volume":"32","author":"Bhatia","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.stem.2018.02.011","article-title":"Organs-on-a-chip: A fast track for engineered human tissues in drug development","volume":"22","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41568-018-0104-6","article-title":"Modelling cancer in microfluidic human organs-on-chips","volume":"19","author":"Hassell","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-bioeng-090120-094330","article-title":"Engineering vascularized organoid-on-a-chip models","volume":"23","author":"Shirure","year":"2021","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1039\/D0LC01186J","article-title":"Vascularized organoids on a chip: Strategies for engineering organoids with functional vasculature","volume":"21","author":"Zhang","year":"2021","journal-title":"Lab Chip"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Huang, C.B.X., and Tu, T.Y. (2023). Recent advances in vascularized tumor-on-a-chip. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1150332"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115986","DOI":"10.1016\/j.bios.2023.115986","article-title":"Vascularized tumor-on-chip microplatforms for the studies of neovasculature as hope for more effective cancer treatments","volume":"249","author":"Konopka","year":"2024","journal-title":"Biosens. Bioelectron."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00240","DOI":"10.1002\/mabi.202500240","article-title":"Vascularized Tumor-on-a-Chip Model as a Platform for Studying Tumor-Microenvironment-Drug Interaction","volume":"25","author":"Kim","year":"2025","journal-title":"Macromol. Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1039\/D5LC01060H","article-title":"Engineering perfusion to meet tumor biology: Are vascularized tumor-on-a-chip models ready to drive therapy innovation?","volume":"26","author":"Poljak","year":"2026","journal-title":"Lab Chip"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1039\/D5LC00890E","article-title":"Vascularizing organoids-on-chip for perfused and personalized models","volume":"26","author":"Menzani","year":"2026","journal-title":"Lab Chip"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189597","DOI":"10.1016\/j.bbcan.2026.189597","article-title":"Functional vasculature in tumor organoids: Enabling precision medicine in oncology","volume":"1881","author":"Wu","year":"2026","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107673","DOI":"10.1016\/j.vph.2026.107673","article-title":"Vascularized tumor organoids as models for interpreting therapeutic response","volume":"164","author":"Huang","year":"2026","journal-title":"Vasc. Pharmacol."},{"key":"ref_25","first-page":"295","article-title":"The environment and disease: Association or causation?","volume":"58","author":"Hill","year":"1965","journal-title":"Proc. R. Soc. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Parkkinen, V.P., Wallmann, C., Wilde, M., Clarke, B., Illari, P., Kelly, M.P., Norell, C., Russo, F., Shaw, B., and Williamson, J. (2018). Evaluating Evidence of Mechanisms in Medicine: Principles and Procedures, Springer.","DOI":"10.1007\/978-3-319-94610-8"},{"key":"ref_27","first-page":"1866","article-title":"Triangulation in aetiological epidemiology","volume":"45","author":"Lawlor","year":"2016","journal-title":"Int. J. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A scale for the quality assessment of narrative review articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1039\/b612140c","article-title":"PDMS absorption of small molecules and consequences in microfluidic applications","volume":"6","author":"Toepke","year":"2006","journal-title":"Lab Chip"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbrc.2016.11.062","article-title":"Small molecule absorption by PDMS in the context of drug response bioassays","volume":"482","author":"Firth","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.bios.2014.07.029","article-title":"Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices","volume":"63","author":"Halldorsson","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1039\/c2lc20982a","article-title":"Engineers are from PDMS-land, biologists are from Polystyrenia","volume":"12","author":"Berthier","year":"2012","journal-title":"Lab Chip"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1021\/ac061990v","article-title":"Characterization and resolution of evaporation-mediated osmolality shifts that constrain microfluidic cell culture in poly(dimethylsiloxane) devices","volume":"79","author":"Heo","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nbt.2958","article-title":"3D bioprinting of tissues and organs","volume":"32","author":"Murphy","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1126\/science.aav9750","article-title":"Multivascular networks and functional intravascular topologies within biocompatible hydrogels","volume":"364","author":"Grigoryan","year":"2019","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.tibtech.2016.03.002","article-title":"Vascularization and angiogenesis in tissue engineering: Beyond creating static networks","volume":"34","author":"Rouwkema","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41596-019-0144-8","article-title":"Microfabricated blood vessels for modeling the vascular transport barrier","volume":"14","author":"Polacheck","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2200143","DOI":"10.1002\/smtd.202200143","article-title":"A robust method for perfusable microvascular network formation in vitro","volume":"6","author":"Wan","year":"2022","journal-title":"Small Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1039\/C1LC20817A","article-title":"Bubbles no more: In-plane trapping and removal of bubbles in microfluidic devices","volume":"12","author":"Lochovsky","year":"2012","journal-title":"Lab Chip"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/s41467-024-45710-4","article-title":"A microfluidic platform integrating functional vascularized organoids-on-chip","volume":"15","author":"Quintard","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mvr.2018.11.007","article-title":"Comparison of organ-specific endothelial cells in terms of microvascular formation and endothelial barrier functions","volume":"122","author":"Uwamori","year":"2019","journal-title":"Microvasc. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4161\/19336918.2014.970001","article-title":"Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model","volume":"8","author":"Buchanan","year":"2014","journal-title":"Cell Adhes. Migr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"766","DOI":"10.7150\/thno.95334","article-title":"Vascularized tumor on a microfluidic chip to study mechanisms promoting tumor neovascularization and vascular targeted therapies","volume":"15","author":"Skubal","year":"2025","journal-title":"Theranostics"},{"key":"ref_44","first-page":"649","article-title":"Lung tumor microphysiological system with 3D endothelium to evaluate modulators of T-cell migration","volume":"40","author":"Wisdom","year":"2023","journal-title":"ALTEX"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1039\/D4LC01089B","article-title":"Vascularized tumor-on-a-chip to investigate immunosuppression of CAR-T cells","volume":"25","author":"Bains","year":"2025","journal-title":"Lab Chip"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1038\/s41467-024-48864-3","article-title":"Roadblocks confronting widespread dissemination and deployment of Organs on Chips","volume":"15","author":"Alver","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_47","unstructured":"U.S. Food and Drug Administration (2026, August 01). Roadmap to Reducing Animal Testing in Preclinical Safety Studies, Available online: https:\/\/www.fda.gov\/files\/newsroom\/published\/roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf."},{"key":"ref_48","unstructured":"CEN-CENELEC Focus Group Organ-on-Chip (2024). Focus Group Organ-on-Chip Standardization Roadmap, CEN-CENELEC. Available online: https:\/\/www.cencenelec.eu\/media\/publication-july-2024-fg-ooc-roadmap.pdf."},{"key":"ref_49","unstructured":"U.S. Food and Drug Administration (2026, August 01). Context of Use, Available online: https:\/\/www.fda.gov\/drugs\/biomarker-qualification-program\/context-use."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"120125","DOI":"10.1016\/j.biomaterials.2020.120125","article-title":"Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids","volume":"254","author":"Kassis","year":"2020","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"Biffi","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","article-title":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1158\/2159-8290.CD-18-0710","article-title":"IL1-induced JAK\/STAT signaling is antagonized by TGF-\u03b2 to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma","volume":"9","author":"Biffi","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.actbio.2025.05.038","article-title":"Deciphering pericyte-induced temozolomide resistance in glioblastoma with a 3D microphysiological system mimicking the biomechanical properties of brain tissue","volume":"200","author":"Maity","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41587-022-01397-w","article-title":"Uncovering the mode of action of engineered T cells in patient cancer organoids","volume":"41","author":"Dekkers","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1158\/2326-6066.CIR-23-1011","article-title":"TBK1 targeting is identified as a therapeutic strategy to enhance CAR T-cell efficacy using patient-derived organotypic tumor spheroids","volume":"13","author":"Sun","year":"2025","journal-title":"Cancer Immunol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1007\/s10439-023-03177-2","article-title":"Evaluation of the morphological and biological functions of vascularized microphysiological systems with supervised machine learning","volume":"51","author":"Tronolone","year":"2023","journal-title":"Ann. Biomed. Eng."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nmeth.4397","article-title":"Data-analysis strategies for image-based cell profiling","volume":"14","author":"Caicedo","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10456-026-10061-9","article-title":"Characterizing pancreatic cancer-associated fibroblast heterogeneity in vascular microphysiological systems","volume":"29","author":"Blackledge","year":"2026","journal-title":"Angiogenesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"119547","DOI":"10.1016\/j.biomaterials.2019.119547","article-title":"Vascularized cancer on a chip: The effect of perfusion on growth and drug delivery of tumor spheroid","volume":"229","author":"Nashimoto","year":"2020","journal-title":"Biomaterials"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"045016","DOI":"10.1088\/1758-5090\/acef99","article-title":"3D vascularized microphysiological system for investigation of tumor\u2013endothelial crosstalk in anti-cancer drug resistance","volume":"15","author":"Kim","year":"2023","journal-title":"Biofabrication"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2410659","DOI":"10.1002\/advs.202410659","article-title":"ODSEI chip: An open 3D microfluidic platform for studying tumor spheroid\u2013endothelial interactions","volume":"12","author":"Ro","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1158\/2159-8290.CD-23-0050","article-title":"Colorectal cancer organoid\u2013stroma biobank allows subtype-specific assessment of individualized therapy responses","volume":"13","author":"Farin","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2402757","DOI":"10.1002\/advs.202402757","article-title":"Personalized vascularized models of breast cancer desmoplasia reveal biomechanical determinants of drug delivery to the tumor","volume":"11","author":"Offeddu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ccell.2022.01.004","article-title":"Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer","volume":"40","author":"Nicolas","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","article-title":"Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma","volume":"21","author":"Provenzano","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.ccr.2014.04.021","article-title":"Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma","volume":"25","author":"Rhim","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.ccr.2014.04.005","article-title":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","volume":"25","author":"Carstens","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1126\/science.abc3734","article-title":"Human microphysiological systems for drug development","volume":"373","author":"Roth","year":"2021","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1021\/acsnano.7b00824","article-title":"Microfluidics enabled bottom-up engineering of 3D vascularized tumor for drug discovery","volume":"11","author":"Agarwal","year":"2017","journal-title":"ACS Nano"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1039\/C8LC00596F","article-title":"Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids","volume":"18","author":"Shirure","year":"2018","journal-title":"Lab Chip"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1039\/D0LC01216E","article-title":"An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy","volume":"21","author":"Hachey","year":"2021","journal-title":"Lab Chip"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1021\/acsbiomaterials.1c01099","article-title":"Vascularized tumor spheroid-on-a-chip model verifies synergistic vasoprotective and chemotherapeutic effects","volume":"8","author":"Hu","year":"2022","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.trsl.2022.11.011","article-title":"A human vascularized microtumor model of patient-derived colorectal cancer recapitulates clinical disease","volume":"255","author":"Hachey","year":"2023","journal-title":"Transl. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2412815","DOI":"10.1002\/adma.202412815","article-title":"Personalized vascularized tumor organoid-on-a-chip for tumor metastasis and therapeutic targeting assessment","volume":"37","author":"Du","year":"2025","journal-title":"Adv. Mater."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/s41587-025-02845-z","article-title":"A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors","volume":"44","author":"Liu","year":"2026","journal-title":"Nat. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10544-025-00748-z","article-title":"A 3D vascularized tumor spheroid microfluidic platform for head and neck cancer research: New insights","volume":"27","author":"Bang","year":"2025","journal-title":"Biomed. Microdevices"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101741","DOI":"10.1016\/j.mtbio.2025.101741","article-title":"A vascularized tumors-on-a-chip model for studying tumor-angiogenesis interplay, heterogeneity and drug responses","volume":"32","author":"Shin","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"218110","DOI":"10.1016\/j.canlet.2025.218110","article-title":"A novel dual-effect bimodal chip cancer research platform: Chips system interconnected vascularized tumor organoids culture with real-time exploration and detection from bench to bedside","volume":"640","author":"Ruan","year":"2026","journal-title":"Cancer Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"102873","DOI":"10.1016\/j.xcrm.2026.102873","article-title":"Self-assembly of tumor-related vascularized colorectal tumoroid-on-a-chip for precision medicine drug testing","volume":"7","author":"Dai","year":"2026","journal-title":"Cell Rep. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11998","DOI":"10.1038\/s41598-017-12049-4","article-title":"Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue\u20132D endothelium interactions and drug screening in co-culture models","volume":"7","author":"Ayuso","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5729","DOI":"10.1038\/s41598-023-31352-x","article-title":"The impact of pericytes on the stability of microvascular networks in response to nanoparticles","volume":"13","author":"Dibble","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1038\/s41598-018-21075-9","article-title":"A microvascularized tumor-mimetic platform for assessing anti-cancer drug efficacy","volume":"8","author":"Pradhan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6855","DOI":"10.1038\/s41598-022-10849-x","article-title":"Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model","volume":"12","author":"Riddle","year":"2022","journal-title":"Sci. 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