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Review

Nature Reviews Cancer 5, 713–725 (1 September 2005) | doi:10.1038/nrc1697

Urothelial tumorigenesis: a tale of divergent pathways

Xue-Ru Wu

Urothelial carcinoma of the bladder is unique among epithelial carcinomas in its divergent pathways of tumorigenesis. Low-grade papillary tumours rarely become muscle-invasive and they frequently harbour gene mutations that constitutively activate the receptor tyrosine kinase–Ras pathway. By contrast, most high-grade invasive tumours progress to life-threatening metastases and have defects in the p53 and the retinoblastoma protein pathways. Correcting pathway-specific defects represents an attractive strategy for the molecular therapy of urothelial carcinomas.