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