Targeting Epigenome As An Innovative Pharmacological Strategy For Castration-resistant Prostate Cancer
Articolo
Data di Pubblicazione:
2016
Citazione:
Targeting Epigenome As An Innovative Pharmacological Strategy For Castration-resistant Prostate Cancer / L. Casati, F. Celotti, V. Sibilia. - In: CLINICAL CANCER DRUGS. - ISSN 2212-697X. - 3:1(2016), pp. 23-35. [10.2174/2212697X03666151207185452]
Abstract:
Background: The importance of epigenetics in cancer is well known. Since
many epigenetic mechanisms are involved in cancer progression, they may represent a target
for a new pharmacological approach. Prostate cancer is the most common malignancy in
men. After failure of the androgen deprivation therapy, the recurrent disease is termed castration-
resistant cancer (CRPC). Since CRPC remains an incurable disease, new studies are
focusing on the mechanisms critical for CRPC development, to identify new pharmacological targets.
Methods: A MEDLINE research related to CRPC and epigenome has been carried out.
Results: CRPC is probably due to several genetic and epigenetic mechanisms involved in AR activation, even
in the presence of low androgen levels. Increasing evidence suggests that an aberrant DNA methylation may
promote CRPC progression, augmenting genomic instability. Deregulated miRNAs are involved in initiation,
progression, and metastatization of prostate cancers. MiRNAs may act like oncogenes (oncomirs) which can
promote cancer progression, or tumor suppressors (anti-oncomirs) which inhibit CRPC progression. miRNA
replacement therapy represents the most promising anticancer strategy, however only MRX34 (a doublestranded
RNA mimic of the anti-oncomir, miR-34) has reached phase I clinical trial. Also, the deregulation of
long non coding RNAs (lncRNAs) has been involved in CRPC development and lncRNAs may gain diagnostic/
therapeutic relevance. Recently research was focused on the chromatin reader proteins containing bromodomain
and extraterminal domain (BET family). Since BET inhibitors act downstream of AR, these compounds
might be effective in a condition of mediated AR resistance to androgen deprivation.
Conclusions: The recent finding about CRPC epigenome might provide several emerging treatment strategies
to counteract efficiently the tumor progression.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Epigenetic; CRPC; androgen receptor; ncRNA; pharmacological approach; BET therapy
Elenco autori:
L. Casati, F. Celotti, V. Sibilia
Link alla scheda completa: