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The limited sensitivity and efficiency of conventional drug screening methods create a pressing need for novel anti\u2010cancer drug screening platforms. This study developed a drug efficacy assessment platform that integrates patient\u2010derived gastric cancer organoids, atomic force microscopy (AFM)\u2010based nanomechanical vibration detection, deep learning analysis and an organoid mechanical model. The platform enables non\u2010destructive detection of intrinsic nano\u2010vibrations of organoids, revealing that their amplitude and spectral characteristics are sensitive to the cytoskeleton, cell\u2010cell junctions, and cellular metabolism. Through the optimization of a deep learning model, we achieved high\u2010precision classification of organoids under pharmacological perturbation. The classification requires only 0.1 s of vibration data and achieves an overall accuracy of 97%. Applied to gastric cancer organoids, our platform detected the effects of picomolar (pM) concentrations of paclitaxel, notably preceding any observable morphological changes or apoptosis signals. Furthermore, the organoid mechanical model accurately predicted drug\u2010induced alterations in both the nanomechanical vibration amplitude and spectrum. These findings validate the platform's advantage for the highly sensitive, non\u2010destructive, and efficient screening of anti\u2010cancer drugs. Collectively, this work establishes a paradigm for organoid\u2010based drug evaluation through dynamic biophysical profiling and holds promise for advancing personalized cancer treatment strategies.<\/jats:p>","DOI":"10.1002\/advs.76878","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:42:01Z","timestamp":1786466521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering Anti\u2010Cancer Drug Efficacy Through Nanomechanical Vibrations in Living Gastric Cancer Organoids"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-7689","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Modern Mechanics CAS Key Laboratory of Mechanical Behavior and Design of Material University of Science and Technology of China  Hefei 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