Role of Chromatin Modifying Complexes and Therapeutic Opportunities in Bladder Cancer

Background: Chromatin modifying enzymes, mainly through post translational modifications, regulate chromatin architecture and by extension the underlying transcriptional kinetics in normal and malignant cells. Muscle invasive bladder cancer (MIBC) has a high frequency of alterations in chromatin modifiers, with 76% of tumors exhibiting mutation in at least one chromatin modifying enzyme [1]. Additionally, clonal expansion of cells with inactivating mutations in chromatin modifiers has been identified in the normal urothelium, pointing to a currently unknown role of these proteins in normal bladder homeostasis.

Objective: To review current knowledge of chromatin modifications and enzymes regulating these processes in Bladder cancer (BCa).

Methods: By reviewing current literature, we summarize our present knowledge of external stimuli that trigger loss of equilibrium in the chromatin accessibility landscape and emerging therapeutic interventions for targeting these processes.

Results: Genetic lesions in BCa lead to altered function of chromatin modifying enzymes, resulting in coordinated dysregulation of epigenetic processes with disease progression.

Conclusion: Mutations in chromatin modifying enzymes are wide-spread in BCa and several promising therapeutic targets for modulating activity of these genes are currently in clinical trials. Further research into understanding how the epigenetic landscape evolves as the disease progresses, could help identify patients who might benefit the most from these targeted therapies.