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In this study, 7\u2010ethyl\u20109\u2010fluorocamptothecin (A2), a camptothecin derivative, which\u00a0demonstrates\u00a0potent tumor\u2010suppressive effects across cellular models, patient\u2010derived organoids (PDOs), and cell line\u2010derived xenograft\/patient\u2010derived xenograft (CDX\/PDX) models is identified. Through pull\u2010down\/mass spectrometry analysis, MAD2L1 is identified as the direct target of A2. A2 specifically binds to the Lys73 site of MAD2L1, activating the cGAS\u2010STING pathway and thereby inducing apoptosis in bladder cancer cells. To address the dose\u2010limiting toxicity caused by A2's insufficient targeting capability, LZU\u2010WZLYCS01, a novel FGFR3\u2010targeting ADC for bladder cancer with A2 as its cytotoxic payload is developed. LZU\u2010WZLYCS01\u00a0exhibits\u00a0precise FGFR3\u2010dependent targeting, with significantly\u00a0reduced\u00a0antitumor activity in both FGFR3\u2010knockout cell models and xenograft models. Moreover,\u00a0in vivo fluorescence imaging demonstrates the potent tumor\u2010targeting capability of LZU\u2010WZLYCS01. LZU\u2010WZLYCS01\u00a0demonstrates\u00a0remarkable bystander effects in an\u00a0in vitro\u00a0co\u2010culture model, along with potent tumor growth inhibition in PDOs and CDX\/PDX models while\u00a0maintaining\u00a0favorable safety. Notably, LZU\u2010WZLYCS01\u00a0shows superior antitumor efficacy to gemcitabine\u2010cisplatin (GC) chemotherapy and maintains\u00a0significant activity in GC\u2010resistant PDX models. These findings\u00a0present\u00a0a promising therapeutic candidate for targeted bladder cancer treatment.<\/jats:p>","DOI":"10.1002\/advs.202509933","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:05:28Z","timestamp":1761894328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel FGFR3\u2010Targeting Antibody\u2010Drug Conjugate Induces Tumor Cell Apoptosis through the cGAS\u2013STING Pathway in Bladder Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Shu","family":"Cui","sequence":"first","affiliation":[{"name":"Institute of Urology The Second Hospital of Lanzhou University Gansu Province Clinical Research Center for Urinary System Disease  Lanzhou 730030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfei","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Lanzhou University  Lanzhou 730030 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