The role of stromal components in urothelial cancer

Bladder cancer (BC) is the most common malignancy of the urinary tract and the ninth most commonly diagnosed cancer worldwide. The incidence of BC varies from region to region and country to country. More than 90% of BCs in Europe and North America are transitional cell carcinomas (TCC), originating from the urothelium or inner wall of the bladder. Approximately 75% of patients with BC show disease confined to the mucosa (stage Ta, CIS) or submucosa (stage T1). These categories are grouped as non-muscle-invasive bladder cancer (NMIBC). Up to 70% of NMIBC cases will recur, and 15% will progress in stage and grade. Therefore, patients with early stage BC are advised and scheduled for frequent monitoring, currently based on cystoscopy and cytology, making BC one of the most expensive cancers to treat. While solid tumors typically arise from the epithelial cells, the surrounding stroma is recognized as an important factor in the process of carcinogenesis and as a driver of cancer progression. In this project, we would then look for stromal components and their impact on the microenvironment of bladder tumors. For example, Fibroblast activation protein-α (FAP) is a transmembrane peptidase that is expressed on stromal cells and acts as a surrogate marker for cancer-associated fibroblasts (CAFs), which are key players in determining the tumor microenvironment. FAP overexpression in CAFs has been associated with therapy resistance in solid tumors such as colorectal, pancreatic and gastric cancer. Today, next-generation sequencing (NGS) has revolutionized oncology by providing diagnostic, prognostic and therapy response biomarkers to support precision medicine. Integration of NGS with other advanced technologies could help to characterize bladder tumors as well. Surrounding aspects such as the immune system, the stromal component, the microbiome and the urobiome; all together could impact the clinical outcomes of NMBICs, notably in terms of BCG responsiveness.