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

Abstract

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.

Toll-Like Receptors Serve as Biomarkers for Early Diagnosis and Prognosis Assessment of Kidney Renal Clear Cell Carcinoma by Influencing the Immune Microenvironment: Comprehensive Bioinformatics Analysis Combined With Experimental Validation

“…KIRC can be cured in early diagnosis, but when the disease is metastatic, it is the cancer with the worst prognosis in the urinary system (Angulo et al, 2021). Therefore, early diagnosis of KIRC is important for its therapeutic efficacy and prognosis.…”

Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

“…ccRCC is not susceptible to chemoradiotherapy ( 3 ). Although ccRCC is curable at an early localized stage by partial or total surgical nephrectomy, advanced or metastatic ccRCC remains a clinical challenge ( 4 ). Over the past years, antiangiogenic treatment, inhibitors of the mammalian target of rapamycin (mTOR) pathway, or immune checkpoint inhibition therapy have considerably evolved ( 5 ).…”

Effects of HMGA2 gene silencing on cell cycle and apoptosis in the metastatic renal carcinoma cell line ACHN

“…The dysregulation of the cell cycle and the inhibition of apoptosis are the key factors that make the treatment of renal carcinoma difficult. 14 , 31 , 32 Therefore, the present study aimed to further investigate the effect of the HMGA2 gene on the biological characteristics of renal carcinoma, so as to clarify the molecular mechanism of its oncogenic effect.…”