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Therefore, timely identification of resistant cases and the provision of alternative therapeutic options are urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A large\u2010scale patient\u2010derived organoid model was established from locally advanced patients with ESCC who underwent perioperative chemotherapy and was validated for consistency with the parental tumours through histopathological, genomic and transcriptomic analysis. A novel two\u2010step drug screening method based on growth rate inhibition (GR) was developed, and drug sensitivity results were compared with clinical outcomes. Additionally, in vivo assays were conducted to evaluate alternative therapies using the\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      \/GR100 index.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ESCC organoids demonstrated high consistency with parental tumours in histopathology, genomics and transcriptomics. The two\u2010step drug screening method revealed a strong correlation with clinical responses (sensitivity 80%, specificity 85.7%, overall accuracy 83.3%) and significantly shortened the experimental timeline compared with the traditional drug screening method (23.08\u00a0\u00b1\u00a02.42 days vs. 45.75\u00a0\u00b1\u00a07.19 days,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). Furthermore, we proposed a novel drug selection strategy based on\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      \/GR100 values, which provides a theoretical foundation for drug repurposing and offers alternative treatment options for patients resistant to TP (taxol\u00a0+\u00a0cisplatin) therapy, thereby facilitating precise re\u2010treatment in drug\u2010resistant subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This method exhibits strong clinical applicability, supporting more accurate and timely decision\u2010making in ESCC management. The\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      \/GR100\u2010based drug screening strategy can dynamically identify alternative sensitive drugs for patients who fail first\u2010line therapies, enabling precise re\u2010treatment. This approach provides a valuable tool for translating laboratory findings into clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70534","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T07:05:48Z","timestamp":1763708748000},"source":"Crossref","is-referenced-by-count":6,"title":["Organoid\u2010based two\u2010step drug screening for rapid identification of chemotherapy\u2010resistant oesophageal squamous cell carcinoma and alternative therapies"],"prefix":"10.1002","volume":"15","author":[{"given":"Chen\u2010Ye","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"Department of Thoracic Surgery, Institute of Minimally Invasive Thoracic Cancer Therapy and Translational Research The First Affiliated Hospital of Soochow University  Suzhou 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