title: Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery.
abstract: BACKGROUND
  Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.
  
  
  METHODS
  This paper provides critical information on existing in vitro and in vivo models to screen the efficacy and toxicity of innovative UBC therapies and point out the challenges for new and improved models.
  
  
  CONCLUSIONS
  In our opinion, results obtained with in vitro and in vivo models should be interpreted together, as a set of delicate biological tools that can be used at different stages in the drug discovery process, to address specific questions. With the development of new technologies, new assays and biomarkers are going to play an important role in the study of UBC. The molecular diagnostics and genomic revolution will not only help to develop new drug therapies, but also to achieve tailored therapies.
authors.affiliation: a Department of Veterinary Sciences , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.|b Center for Research and Technology of Agro-Environment and Biological Sciences , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.
authors.forename: P A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: e Faculty of Engineering, Laboratory for Process, Environment, Biotechnology and Energy Engineering (LEPABE) , University of Porto , Porto , Portugal.|f Molecular Oncology and Viral Pathology Group , Portuguese Institute of Oncology , Porto , Portugal.
authors.forename: R M
authors.initials: RM
authors.lastname: Gil da Costa
authors.affiliation: g Instituto Politécnico de Viseu , Escola Superior Agrária de Viseu , Viseu , Portugal.|h CECA , Universidade do Porto , Porto , Portugal.|j Experimental Pathology and Therapeutics Group , Portuguese Institute of Oncology , Porto , Portugal .
authors.forename: C
authors.initials: C
authors.lastname: Vasconcelos-Nóbrega
authors.affiliation: b Center for Research and Technology of Agro-Environment and Biological Sciences , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.|c QOPNA, Mass Spectrometry Center, Department of Chemistry , University of Aveiro , Aveiro , Portugal.|d Laboratory Animal Science Group , Institute for Research and Innovation in Health (I3S) , Porto , Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Arantes-Rodrigues
authors.affiliation: i Cytogenetic Laboratory, Department of human genetics , Hospital center of Trás-os-Montes and Alto Douro , Vila Real , Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Pinto-Leite
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008958:Models, Molecular; D025202:Molecular Diagnostic Techniques; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Animal models; antineoplastic drugs; cell culture; treatment; tumor; urothelial