Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Animal models
• antineoplastic drugs
• cell culture
• treatment
• tumor
• urothelial

Article highlights

• A variety of in vitro and in vivo models exist for urinary bladder cancer research.

• Different models have different uses and limitations: it is therefore very important to choose carefully.

• 3D and organotypic cell culture techniques are refining in vitro approaches.

• A wide-spectrum characterization of available in vivo models is needed.

• Complementary models provide a comprehensive and realistic view of each problem.

• Despite the advances made over the years, there are still many challenges to overcome in in vitro models.

This box summarizes key points contained in the article.

Declaration of interest

This work is supported by: European Investment Funds by FEDER/COMPETE/POCI- Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and Project POCI-01-0145-FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy - LEPABE funded by FEDER funds through COMPETE2020) and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. R.M. Gil da Costa was supported by FCT grant number SFRH/BPD/85462/2012. R. Arantes-Rodrigues was supported by FCT grant number SFRH/BPD/101700/2014. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.