{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:21:17Z","timestamp":1789168877774,"version":"build-2803163510"},"reference-count":141,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China Young Scientists Fund","award":["32501158"],"award-info":[{"award-number":["32501158"]}]},{"name":"Start-up Fundings of Ocean University of China","award":["862401013154"],"award-info":[{"award-number":["862401013154"]}]},{"name":"Start-up Fundings of Ocean University of China","award":["862401013155"],"award-info":[{"award-number":["862401013155"]}]},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center","award":["LMDBCXRC202401"],"award-info":[{"award-number":["LMDBCXRC202401"]}]},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center","award":["LMDBCXRC202402"],"award-info":[{"award-number":["LMDBCXRC202402"]}]},{"name":"Taishan Scholar Youth Expert Program of Shandong Province","award":["tsqn202306102"],"award-info":[{"award-number":["tsqn202306102"]}]},{"name":"Taishan Scholar Youth Expert Program of Shandong Province","award":["tsqn202312105"],"award-info":[{"award-number":["tsqn202312105"]}]},{"name":"Shandong Provincial Overseas Excellent Young Scholar Program","award":["2024HWYQ-042"],"award-info":[{"award-number":["2024HWYQ-042"]}]},{"name":"Shandong Provincial Overseas Excellent Young Scholar Program","award":["2024HWYQ-043"],"award-info":[{"award-number":["2024HWYQ-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mechano-Organ-on-Chip (Mechano-OoC) platforms are emerging as powerful microphysiological systems that place mechanical cues at the center of tumor modeling, providing a scalable and human-relevant approach to recapitulate the biophysical complexity of the tumor microenvironment. Mechanical factors such as matrix stiffness, viscoelasticity, solid stress, interstitial flow, confinement, and shear critically regulate cancer progression, metastasis, immune interactions, and treatment response, yet remain poorly captured by conventional in vitro models and are often studied separately in tumor-on-chip and mechanobiology research. In this review, we summarize recent advances in mechano-OoC technologies for cancer research, highlighting strategies that integrate engineered mechanical cues with microfluidics, tunable extracellular matrices, vascular and stromal interfaces, and dynamic loading to model tumor invasion, vascular transport, immune trafficking, and drug delivery. We also discuss emerging approaches for real-time, multimodal readouts, including sensor-integrated platforms and artificial intelligence-assisted data analysis, and outline key challenges that limit translation, such as device complexity, limited throughput, insufficient standardization, and inadequate validation against in vivo and clinical data. By organizing progress across platform engineering, sensing and readout, data standardization, and AI-driven analytics, this review provides a unified framework for advancing mechanobiology-aware tumor models and guiding the development of predictive preclinical platforms for precision cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms27031330","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:12:23Z","timestamp":1769674343000},"page":"1330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechano-Organ-on-Chip for Cancer Research"],"prefix":"10.3390","volume":"27","author":[{"given":"Luyang","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7446-0569","authenticated-orcid":false,"given":"James Chung Wai","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9167-0840","authenticated-orcid":false,"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1100-9994","authenticated-orcid":false,"given":"Bee Luan","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China"},{"name":"Hong Kong Centre of Cerebro-Cardiovascular Health Engineering (COCHE), Shatin, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-4599","authenticated-orcid":false,"given":"Siu Hong Dexter","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marrella, A., Fedi, A., Varani, G., Vaccari, I., Fato, M., Firpo, G., Guida, P., Aceto, N., and Scaglione, S. 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