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

Sep 22, 2026

Rapid establishment of KRAS-driven bladder cancer initiation and immune escape models combines a gene expression mouse model (GEMM) with advanced organoid technology. Longitudinal monitoring is performed with single-cell sequencing to capture tumor evolution, cellular dynamics, and communication networks. The resulting platform recapitulates key single-cell molecular features seen in human bladder cancer and is designed to support scalable, physiologically relevant preclinical drug screening. This integrated framework addresses limits of conventional models and strengthens investigation of tumor origin, progression, and immune escape.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Methods

Results

Discussion

Keywords

TYPE Original Research PUBLISHED 23 March 2026 DOI 10.3389/fimmu.2026.1726443 OPEN ACCESS EDITED BY Chun-Wai Mai, IMU University, Malaysia REVIEWED BY Hongda Zhao, The Chinese University of Hong Kong, China Qiang Li, University at Buffalo, United States *CORRESPONDENCE Guoliang Yang [ygl0511@126.com](ygl0511@126.com)[ ](ygl0511@126.com)Mengyao Liu [liumengyao@renji.com](liumengyao@renji.com)[ ](liumengyao@renji.com)Bin Yu [yubinrenji@outlook.com](yubinrenji@outlook.com)[ ](yubinrenji@outlook.com)†These authors have contributed equally to this work RECEIVED 20 October 2025 REVISED 27 February 2026 ACCEPTED 28 February 2026 PUBLISHED 23 March 2026 CITATION Yang G, Wang Y, Fan Z, Wei G, Shen X, Zhang HJ, Liu M and Yu B (2026) Rapid establishment of KRAS-driven bladder cancer initiation and immune escape models using genetically engineered mice and organoid approaches. Front. Immunol. 17:1726443 . doi: 10.3389/fimmu.2026.1726443 COPYRIGHT © 2026 Yang, Wang, Fan, Wei, Shen, Zhang, Liu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Rapid establishment of KRASdriven bladder cancer initiation and immune escape models using genetically engineered mice and organoid approaches Guoliang Yang 1*†, Yishu Wang 2†, Zhangzhengyi Fan 1†, Guojiang Wei 1†, Xuqing Shen 3, HeJian Zhang 1, Mengyao Liu 1* and Bin Yu 4,5* 1 Department of Urology Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2 Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 3 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China, 4State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, 5Shanghai Key Laboratory for Cancer Systems Regulation and Clinical Translation (CSRCT), Shanghai, China 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. KEYWORDS bladder cancer, genetically engineered mouse model (GEMM), KRAS oncogene, organoid culture, tumor immune escape Introduction Bladder cancer is the 10th most common cancer worldwide and the 6th most prevalent in men (1, 2) . It is clinically categorized into non-muscle-invasive (NMIBC) and muscleinvasive (MIBC) disease. Although NMIBC generally has a favorable prognosis, 60-70% of cases recur, and 10-20% progress to MIBC, which is associated with poorer outcomes (3, 4) . The genomic landscape of bladder cancer is marked by signiﬁcant chromosomal instability and frequent alterations in tumor suppressor genes such as TP53, PTEN, a

FAQs

What main goal does the study target?

The study aims to rapidly establish KRAS-driven bladder cancer initiation and immune escape models that better represent human disease biology for downstream research and therapeutic testing.

How are the models built in the study?

An integrated strategy is used, combining a novel GEMM with organoid technology, with tumor behavior tracked longitudinally.

What technique is used to monitor tumor evolution and cellular dynamics?

Single-cell sequencing is applied to monitor tumor evolution and cellular dynamics over time.

Why are these models considered useful for drug development?

The models recapitulate single-cell molecular features and cellular communication networks from human bladder cancer and provide a scalable, physiologically relevant platform for preclinical drug screening.

Sep 22, 2026

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