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Progress made in the use of animal models for the study of high-risk, nonmuscle invasive bladder cancer

Lin-Tsai, Opala; Taylor, John A. IIIb; Clark, Peter E.a; Adam, Rosalyn M.c; Wu, Xue-Rud; DeGraff, David J.e

doi: 10.1097/MOU.0000000000000087

Purpose of review High-risk, nonmuscle invasive bladder cancer (HR-NMIBC) represents a costly and difficult-to-treat disease, the molecular pathogenesis of which has a limited understanding. Most preclinical models for the study of bladder cancer are more appropriate for the study of advanced disease. However, recent key advances in preclinical animal models places us at an opportune position to better understand HR-NMIBC.

Recent findings Discoveries in the basic sciences allow us to better understand tumor biology when building models of bladder cancer. Of note, a key study on urothelial progenitor cells recently highlighted an important role for Sonic hedgehog-positive cells and retinoid signaling that is essential for urothelial development and regeneration. In the translational realm, transgenic mouse models continue to be used, with a recent interest in the role of Wnt/beta-catenin in urothelial carcinomas. Tissue recombination models are also being increasingly utilized to better recreate the tissue microenvironment and better understand stromal–epithelial interactions and the impact of genetic alterations on tissue differentiation. Lastly, the avatar mouse systems, which involve direct xenotransplantation of human tumor specimens into immunocompromised mice, represent an additional approach to study cancer characteristics in a preserved tissue context.

Summary With molecular alterations remaining an unclear area of our understanding of HR-NMIBC, preclinical models of bladder cancer serve as essential tools to discover specific genetic compromises in disease pathogenesis and the therapeutics to treat them.

aSchool of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

bDivision of Urology, University of Connecticut Health Center, Farmington, Connecticut

cDepartment of Urology, Boston Children’s Hospital, and Department of Surgery, Harvard Medical School, Boston, Massachusetts

dDepartment of Urology and Department of Medicine, New York University, New York

eDepartment of Pathology, Pennsylvania State University Cancer Institute, Pennsylvania State University, Hershey, Pennsylvania, USA

Correspondence to David J. DeGraff, PhD, Assistant Professor of Pathology, Pennsylvania State University, College of Medicine, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, PA 17033, USA. Tel: +1 717 531 0003; fax: +1 717 531 5021; e-mail:

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