Tumor Heterogeneity and Phenotypic Plasticity in Bladder Carcinoma

Abstract

Bladder carcinoma is the most common malignancy of the urinary system with a high recurrence rate. As of today, bladder carcinoma does not sufficiently benefit from new therapeutic strategies. The molecularly heterogeneous landscape contributes an enormous challenge in the management of this cancer. Consensus clustering based on gene expression data from muscle-invasive and non-muscle-invasive tumors identified multiple intrinsic molecular subsets of this cancer. In our recent study, we have computed epithelial-mesenchymal transition (EMT) scores of three key bladder cancer subtypes followed by the comparative phosphoproteomics profiling of the molecular subtypes. The most aggressive non-type bladder subtype correlated with a mesenchymal-like phenotype. The improved stratification of the molecular features of these subtypes would provide a new opportunity for a deeper understanding of disease pathogenesis. This review focuses on the concepts of cellular plasticity and heterogeneity in bladder carcinoma. We also raised some of the challenges during the discovery and therapeutic intervention of targeted therapy and its clinical implication.