Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet

Abstract

Bladder cancer (BC) is the most common neoplasia of the urothelial tract. Due to its high incidence, prevalence, recurrence and mortality, it remains an unsolved clinical and social problem. The treatment of BC is challenging and, although immunotherapies have revealed potential benefit in a percentage of patients, it remains mostly an incurable disease at its advanced state. Epigenetic alterations, including aberrant DNA methylation, altered chromatin remodeling and deregulated expression of non-coding RNAs are common events in BC and can be driver events in BC pathogenesis. Accordingly, these epigenetic alterations are now being used as potential biomarkers for these disorders and are being envisioned as potential therapeutic targets for the future management of BC. In this review, we summarize the recent findings in these emerging and exciting new aspects paving the way for future clinical treatment of this disease.

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

“…Alterations in chromatin-modifying genes are frequent in all stages of BLCa, indicating that they can be early genomic alterations [68,70]. The lysine demethylase 6A (KDM6A) is mutated in 60% of low-grade Ta tumors and inhibits H3K27 methyltransferase EZH2 [70,79,83]. Given that EZH2 is often overexpressed and associated with MIBC, KDM6A activity might counteract tumor progression [84].…”

Patient‐derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR‐T cells in vitro

“…Currently, radical cystectomy and platinum‐based chemotherapy are the therapeutic options available for MIBC. However, a large number of patients with MIBC develop metastatic spread, which is associated with extremely low survival rates 4 . Novel approaches such as immunotherapy are currently being investigated.…”

Aberrant DNA Methylation in Bladder Cancer among Saudi Arabia Population

“…[3][4][5][6] Currently, aberrant modification of deoxyribonucleic acid (DNA) methylation patterns of tumor suppressor genes is of particular interest. [3][4][5][6] These aberrant DNA methylation patterns can be detected in blood, urine, or serum of the cancer patient as cfDNA. 2 Although these alterations are dynamic and respond to environmental influences 7 and have been studied worldwide, 8 to date no study has profiled similar alterations in Saudi population of BC patients.…”