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

被引:23
作者
Angulo, Javier C. [1 ,2 ]
Manini, Claudia [3 ]
Lopez, Jose I. [4 ,5 ]
Pueyo, Angel [6 ,7 ]
Colas, Begona [8 ]
Ropero, Santiago [8 ]
机构
[1] European Univ Madrid, Clin Dept, Fac Med Sci, Madrid 28005, Spain
[2] Univ Hosp Getafe, Dept Urol, Madrid 28907, Spain
[3] San Giovanni Bosco Hosp, Dept Pathol, I-10154 Turin, Italy
[4] Cruces Univ Hosp, Dept Pathol, Baracaldo 48903, Spain
[5] BioCruces Bizkaia Hlth Res Inst, Baracaldo 48903, Spain
[6] Innovat Univ Hosp Infanta Leonor & South East, Fdn Biomed Res, Madrid 28003, Spain
[7] UCAM Univ Catolica San Antonio Murcia, Heath Sci PhD Program, Murcia 30107, Spain
[8] Univ Alcala, Dept Syst Biol, Biochem & Mol Biol Unit, Alcala De Henares 28805, Spain
关键词
renal cell carcinoma; biomarker; DNA methylation; epigenetics; HISTONE DEACETYLASE INHIBITOR; CPG ISLAND METHYLATION; PHASE-II TRIAL; ANTISENSE OLIGONUCLEOTIDE MG98; GLOBAL DNA-METHYLATION; TUMOR-SUPPRESSOR GENE; LONG NONCODING RNA; KIDNEY CANCER; PROMOTER METHYLATION; PROGNOSTIC RELEVANCE;
D O I
10.3390/cancers13092071
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary The accumulated evidence on the role of epigenetic markers of prognosis in clear cell renal cell carcinoma (ccRCC) is reviewed, as well as state of the art on epigenetic treatments for this malignancy. Several epigenetic markers are likely candidates for clinical use, but still have not passed the test of prospective validation. Development of epigenetic therapies, either alone or in combination with tyrosine-kinase inhibitors of immune-checkpoint inhibitors, are still in their infancy. 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.
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页数:30
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