{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:14:46Z","timestamp":1784556886972,"version":"3.55.0"},"reference-count":109,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Development Plan Project of Jilin Province","award":["20250206029ZP"],"award-info":[{"award-number":["20250206029ZP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Preclinical bladder cancer models are often judged by tumor take, tumor growth or treatment inhibition, yet these endpoints do not reveal which bladder-specific constraints a given model preserves or bypasses. The bladder is shaped by a specialized urothelial barrier, urine exposure, cyclic filling and emptying, inflammatory injury, metabolic stress and intravesical treatment pressure. In this review, we use susceptibility engineering as an organizing framework for model selection and validation. We define susceptibility engineering as the deliberate definition, perturbation and reporting of model states that alter tumor initiation, adhesion, colonization, survival or therapeutic exposure. This framework groups cell lines, patient-derived organoids, cell-line-derived xenograft (CDX) and patient-derived xenograft (PDX) models, orthotopic transplantation, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced tumors, genetically engineered mouse models and large-animal platforms according to the biological constraints they test. We focus on three linked dimensions: urothelial barrier integrity and uroplakin-related tools; local colonization thresholds under bladder-specific selection; metabolic susceptibility involving peroxisome proliferator-activated receptor gamma (PPARG)-associated differentiation programs and candidate solute carrier family 25 (SLC25)-linked mitochondrial stress nodes. We further distinguish large-animal systems as platforms for local delivery, imaging, device testing and procedural scale rather than universal substitutes for mouse models. A susceptibility-based validation framework could improve model selection, explain divergent responses across systems and support tiered platforms that connect patient-derived biology, mechanistic mouse studies and clinically realistic intravesical evaluation.<\/jats:p>","DOI":"10.3390\/ph19071116","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Models of Bladder Cancer: Barrier, Metabolic, and Translational Susceptibility"],"prefix":"10.3390","volume":"19","author":[{"given":"Tianjia","family":"Liu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Baicheng Medical College, Baicheng 137000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinzhamusu","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Cui","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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