Preclinical Models for Bladder Cancer Research

Abstract

At diagnosis, more than 70% of bladder cancers (BCs) are at the non-muscle-invasive bladder cancer (NMIBC) stages, which are usually treated with transurethral resection followed by intravesical instillation. For the remaining advanced cancers, systemic therapy is the standard of care, with addition of radical cystectomy in cases of locally advanced cancer. Because of the difference in treatment modalities, different models are needed to advance the care of NMIBC and advanced BC. This article gives a comprehensive review of both in vitro and in vivo BC models and compares the advantages and drawbacks of these preclinical systems in BC research.

Keywords: Bladder cancer; Conditionally reprogrammed cell culture; Genetically engineered mouse model; Humanized mouse; Organoid; Patient-derived xenograft.

Figure 1. Organoid models:

Organoids can be developed from clinical cancer specimens, cell lines, or other models. After the initial pathology review and process (mincing and/or digestion), cells or tissues are seeded into culture dishes with supporting materials, such as Matrigel, which then grows in 3D structures and form spheroids. Organoids retain some of the 3D cancer structure and tumor microenvironment and recapitulate some of the cancer behaviors in vivo.

Figure 2. The establishment and identification of PDX.

BC tissues are collected from BC patients, and implanted into immune deficient mice to generate Passage 0 (P0) PDXs. After characterization and validation, P01 PDXs are re-implanted and expanded for cryopreservation and for research use.