Rapid establishment of KRAS-driven bladder cancer initiation and immune escape models using genetically engineered mice and organoid approaches.

Abstract

INTRODUCTION: Bladder cancer is the tenth most common cancer worldwide and the sixth most common among men. However, research into representative tumor models for bladder cancer remains underdeveloped, limiting insights into tumor biology and drug development. METHODS: We developed an integrated approach combining a novel gene expression mouse model (GEMM) with advanced organoid technology. This system was tracked longitudinally using single-cell sequencing to monitor tumor evolution and cellular dynamics. RESULTS: Our model accurately recapitulates the single-cell molecular features and cellular communication networks observed in human bladder cancer. It provides a scalable and physiologically relevant platform for preclinical drug screening. DISCUSSION: This integrated framework offers a new platform for studying tumor origin and evolution, overcoming key limitations of conventional systems and advancing bladder cancer research.