Abstract
Retinoic acid signaling is a crucial developmental pathway involved in urothelium development, differentiation and regeneration. Deregulation of the retinoic acid signaling is highly implicated in several cancers, including bladder cancer, underlying the need to unravel the complete regulatory aspects of the retinoids in bladder tumorigenesis. Given the fact that retinoic acid receptors are transcription factors functioning at the chromatin level and act in close cooperation with chromatin modifiers, it is known that retinoids show their efficacy by changing the epigenome. Bladder cancer can be defined as a 'disease of chromatin' with mutations identified in the genes involved in chromatin regulation in 80% of the patients. Therefore, a careful examination of the epigenetic backgrounds and the breakdown of the emerging and highly underexplored field of retinoic acid dependent regulation of the epigenome is essential to fully understand the retinoid-dependent effects on bladder cancer. With this motivation, in this review, we evaluate the role of retinoic acid signaling in bladder cancer with a focus on the regulatory and mutational aspects, emphasizing the deregulatory characteristics in bladder cancer and highlighting the potential treatment opportunities with the retinoic acid and derivatives alone or in combination with epigenetic drugs.
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