title: Progress made in the use of animal models for the study of high-risk, nonmuscle invasive bladder cancer.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Opal
authors.initials: O
authors.lastname: Lin-Tsai
authors.forename: John A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
authors.forename: Xue-Ru
authors.initials: XR
authors.lastname: Wu
authors.forename: David J
authors.initials: DJ
authors.lastname: DeGraff
mesh_terms: D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000453:epidemiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D053823:Hedgehog Proteins / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000503:physiopathology*; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; D051153:Wnt Proteins; D051176:beta Catenin