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We established patient-derived organoids (PDOs) from 31 clinical BC specimens, achieving an 80.65% success rate. These organoids preserved distinct morphological subtypes: solid, hollow, and mixed and retained stable proliferative capacity. Histological and molecular analyses confirmed that PDOs recapitulated key features of the parental tumors, including a hybrid basal-luminal phenotype with elevated CD44, GATA3, and LGR5 expression, and peripheral localization of CK20 and Uroplakin 3\u00a0A (UPK3A), indicating structural polarity and urothelial differentiation. Functional drug screening of early-passage PDOs revealed heterogeneous responses to standard-of-care (SOC) agents, cisplatin and gemcitabine, as well as the EGFR\/HER2 inhibitor lapatinib. Notably, lapatinib enhanced chemosensitivity in a dose-dependent manner, even at reduced concentrations of standard agents. The most effective combinatorial regimens significantly impaired organoid viability and architecture, suggesting a synergistic effect. Drug response variability across PDO lines correlated with patient-specific clinical features, including tumor grade and recurrence status. These results demonstrate that BC PDOs faithfully model tumor heterogeneity and offer a robust platform for individualized drug response profiling. Our findings support the utility of PDOs for preclinical drug evaluation and precision oncology, particularly in identifying effective combination therapies such as lapatinib-enhanced chemotherapy.<\/jats:p>","DOI":"10.1038\/s41598-026-59564-x","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T11:13:53Z","timestamp":1782558833000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient-derived organoids as a predictive platform for drug sensitivity in bladder cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Shirin","family":"Hekmatirad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Gholizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Montazeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh","family":"Sharifi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Nowroozi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Ali","family":"Hamidieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hosein","family":"Yazdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Mollapour Sisakht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"issue":"10","key":"59564_CR1","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.3390\/cancers13102496","volume":"13","author":"M Pones","year":"2021","unstructured":"Pones, M. et al. 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