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BC has high rates of treatment failure, so alternate approaches are needed to personalise treatments to individual patients in order to improve outcomes from this disease. One method that could provide actionable results to influence clinical decisions on alternative treatments is ex vivo drug screening.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We explored the feasibility of using ex vivo drug screening directly on patient tumour tissue from transurethral resection of the bladder tumours (TURBT) and cystectomies. We screened 38 BC patients investigating drug sensitivities to 15 agents, including standard of care treatments and some more exploratory compounds. In addition, we investigated ex vivo sensitivity and resistance over the 15 compounds and annotated common mutational profiles. We saw high methodological success (41\/54 samples, 75.9%), in clinically useful timeframes (4 days) and identified distinct drug and tumour clusters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we show that drug resistance is associated with aggressive clinical features, mutation burden, and differs with individual gene mutations. Cross-resistance between agents is common. Cisplatin-resistant tumours differ by mutational profiles and include those with multi-drug resistance and those sensitive to alternative agents. Observed clinical responses match our ex vivo response (5\/6 patients, 83.3%). Proliferative responses are observed to some receptor tyrosine kinase inhibitors, cautioning against their unselected widespread use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ex vivo drug screening identifies drug clusters of patients\u2019 tumours that could potentially respond to standard of care and alternative therapies. Our approach offers a platform to potentially individualise treatments, especially in drug-resistant tumours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01596-5","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:43:26Z","timestamp":1778751806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ex vivo drug screening and clustering of bladder cancers for pre-clinical treatment prediction"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-4908","authenticated-orcid":false,"given":"S.","family":"Conroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Gagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-4186","authenticated-orcid":false,"given":"LA","family":"Quayle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JA","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ST","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Helleday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-511X","authenticated-orcid":false,"given":"SA","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-7637","authenticated-orcid":false,"given":"J.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4999-5585","authenticated-orcid":false,"given":"JK","family":"Rantala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-2890","authenticated-orcid":false,"given":"SJ","family":"Danson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JWF","family":"Catto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-9836","authenticated-orcid":false,"given":"G.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"1596_CR1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.eururo.2023.03.029","volume":"84","author":"I Jubber","year":"2023","unstructured":"Jubber, I. et al. 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S.A.H has received research funding from Cancer Research UK, MRC\/NIHR, UHB charities, CCC charities, North-West Cancer Research, Yorkshire Cancer Research, Weston Park Cancer Charity, Bayer, Janssen, Boehringer Ingelheim, Pierre Fabre, Eli Lilly, Roche, and has received advisory board\/consultancy fees from Roche, MSD, AstraZeneca, BMS, Janssen, GSK, Astellas, Pfizer, Bayer, Merck, Pierre Fabre, Sotio, Gilead. JG has received research funding from Roche and in-kind research support from Owkin and has received honoraria from ISSECAM. JKR is the founder of Misvik Biology Ltd and has received research funding from AstraZeneca and Boehringer Ingelheim. SJD has received consulting fees from Orion Therapeutics, Oxcia and Incanthera. JWFC has received consulting fees from AstraZeneca, Ferring, Ipsen, Roche, and Janssen; has received speaker fees from Bristol Myers Squibb, Pfizer, Merck Sharp & Dohme, Janssen, Astellas, Nucleix, InMed, and Roche; has received honoraria for membership in advisory boards from Ferring, Roche, Gilead, Photocure, Pfizer, Bristol Myers Squibb, QED Therapeutics, and Janssen; and has received research funding from Roche. HG, LAQ, STW, TH, RA, and GW have declared no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"417"}}