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 metast...

Full description

Bibliographic Details
Main Authors: Javier C. Angulo, Claudia Manini, Jose I. López, Angel Pueyo, Begoña Colás, Santiago Ropero
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/9/2071
_version_ 1797536373721268224
author Javier C. Angulo
Claudia Manini
Jose I. López
Angel Pueyo
Begoña Colás
Santiago Ropero
author_facet Javier C. Angulo
Claudia Manini
Jose I. López
Angel Pueyo
Begoña Colás
Santiago Ropero
author_sort Javier C. Angulo
collection DOAJ
description 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.
first_indexed 2024-03-10T11:58:48Z
format Article
id doaj.art-41ed8eaad6d249a29adc4641d81bb448
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-10T11:58:48Z
publishDate 2021-04-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-41ed8eaad6d249a29adc4641d81bb4482023-11-21T17:04:12ZengMDPI AGCancers2072-66942021-04-01139207110.3390/cancers13092071The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic TreatmentsJavier C. Angulo0Claudia Manini1Jose I. López2Angel Pueyo3Begoña Colás4Santiago Ropero5Clinical Department, Faculty of Medical Sciences, European University of Madrid, 28005 Madrid, SpainDepartment of Pathology, San Giovanni Bosco Hospital, 10154 Turin, ItalyDepartment of Pathology, Cruces University Hospital, 48903 Barakaldo, SpainFoundation for Biomedical Research, Innovation of University Hospitals Infanta Leonor and South-East, 28003 Madrid, SpainBiochemistry and Molecular Biology Unit, Department of Systems Biology, University of Alcalá, 28805 Alcalá de Henares, SpainBiochemistry and Molecular Biology Unit, Department of Systems Biology, University of Alcalá, 28805 Alcalá de Henares, SpainClear 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.https://www.mdpi.com/2072-6694/13/9/2071renal cell carcinomabiomarkerDNA methylationepigenetics
spellingShingle Javier C. Angulo
Claudia Manini
Jose I. López
Angel Pueyo
Begoña Colás
Santiago Ropero
The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
Cancers
renal cell carcinoma
biomarker
DNA methylation
epigenetics
title The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
title_full The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
title_fullStr The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
title_full_unstemmed The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
title_short The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
title_sort role of epigenetics in the progression of clear cell renal cell carcinoma and the basis for future epigenetic treatments
topic renal cell carcinoma
biomarker
DNA methylation
epigenetics
url https://www.mdpi.com/2072-6694/13/9/2071
work_keys_str_mv AT javiercangulo theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT claudiamanini theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT joseilopez theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT angelpueyo theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT begonacolas theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT santiagoropero theroleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT javiercangulo roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT claudiamanini roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT joseilopez roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT angelpueyo roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT begonacolas roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments
AT santiagoropero roleofepigeneticsintheprogressionofclearcellrenalcellcarcinomaandthebasisforfutureepigenetictreatments