The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments.

Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.

Cancers. 2021 Apr 25*** epublish ***

Javier C Angulo, Claudia Manini, Jose I López, Angel Pueyo, Begoña Colás, Santiago Ropero

Clinical Department, Faculty of Medical Sciences, European University of Madrid, 28005 Madrid, Spain., Department of Pathology, San Giovanni Bosco Hospital, 10154 Turin, Italy., Department of Pathology, Cruces University Hospital, 48903 Barakaldo, Spain., Foundation for Biomedical Research, Innovation of University Hospitals Infanta Leonor and South-East, 28003 Madrid, Spain., Biochemistry and Molecular Biology Unit, Department of Systems Biology, University of Alcalá, 28805 Alcalá de Henares, Spain.