Husna, Amity University Kolkata
Retinoic acid (RA) is a primary bioactive metabolite found in vitamin A. It induces various important effects in cell growth and differentiation for both embryonic development and adult physiology. So, the retinoids have a crucial function in human physiology including fertilization, foetal development, they can also modulate immunity and vision and are very essential for the proper functioning of skin, lung, liver, and neural system. But the mis-regulation of the retinoic acid signalling can cause several cancers, including bladder cancers which is the 5th most common cancer and cause more than 150,000 deaths each year. So, there’s a need to understand the complete regulatory aspect of the retinoids in bladder tumours.
Bladder cancer is also known as ‘disease of chromatin’ as in 80% patients, the mutations occur in the genes which are involved in chromatin regulation. As the retinoic acid receptors function at chromatin level and act in close cooperation with chromatin modifiers, so the retinoids show their effects by changing the epigenome and an excessively high mutational load of the epigenetic machinery in bladder cancer can induce the tumour more. The Retinoic acid (RA) action is mediated by the retinoic acid receptor (RAR). Among the RARs receptors, RARβ2 receptor can regulate the inhibitory activities of RA on cell proliferation. The RARβ2 gene is epigenetically silenced in human cancers which are generally linked with the retinoid resistance. A therapeutic agent for the treatment is ATRA, all-trans-retinoic acid. This is an active metabolite which is generated when dietary-derived Vitamin A is metabolized intracellularly.
Research has revealed the potential of ATRA cancer therapy, especially in bladder cancer. The treatment with ATRA is most effective when used in combination with other epigenetic drugs as it can target sophisticated gene silencing mechanisms as well as modulate anticancer activities. Although this has a prospering clinical effect the proof of retinoid-resistance in some cancers has restricted the clinical use of retinoids. Therefore, to overcome the retinoid resistance an advanced knowledge of RA resistance mechanisms is a must for retinoid-based treatments.
Also read: Vitamin D Receptors In Association To Breasts Cancer
SOURCE:
Retinoic acid signalling and bladder cancer: Epigenetic deregulation, therapy and beyond.
Gizem Ozgun, Serif Sentürk and Serap Erkek-Ozhan , Izmir Biomedicine and Genome Center, Inciralti 35340, Izmir, Turkey. Dokuz Eylül University Izmir International Biomedicine and Genome Institute, Inciralti 35340, Izmir, Turkey.10.1002/ijc.33374
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