2010
DOI: 10.1158/0008-5472.can-09-3427
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Cisplatin is among the most widely used cytotoxic anti-cancer agents in solid tumors, however, the development of secondary resistance remains a major obstacle to clinical efficacy. Treatment-related DNA hypermethylation may play a role in creating drug resistant phenotypes by inactivating genes that are required for cytotoxicity. We applied a pharmacologic unmasking approach to detect hypermethylated genes whose inactivation contributes to cisplatin resistance. Utilizing three pairs of isogeneic, cisplatin-se… Show more

Help me understand this report
View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
2

Citation Types

4
88
0

Year Published

2012
2012
2019
2019

Publication Types

Select...
6
1

Relationship

0
7

Authors

Journals

citations
Cited by 106 publications
(92 citation statements)
references
References 39 publications
4
88
0
Order By: Relevance
“…Our results indicate that several methylation changes are directly associated with chemosensitization induced by demethylating agents combined with HDAC inhibitors. Similar observations have been reported in other tumour types (Chang et al, 2010); however, our data also reveal that epigenetic alterations associated with sensitivity to cisplatin occur at a few selected genes rather than at large numbers of loci in this cell line model (Glasspool et al, 2006). The group of epigenetically inactivated genes was upregulated by DAC and also the combined DAC and Belinostat treatment, but remained unaffected by Belinostat alone, with the exception of GLUL.…”
Section: Discussionsupporting
confidence: 89%
See 2 more Smart Citations
“…Our results indicate that several methylation changes are directly associated with chemosensitization induced by demethylating agents combined with HDAC inhibitors. Similar observations have been reported in other tumour types (Chang et al, 2010); however, our data also reveal that epigenetic alterations associated with sensitivity to cisplatin occur at a few selected genes rather than at large numbers of loci in this cell line model (Glasspool et al, 2006). The group of epigenetically inactivated genes was upregulated by DAC and also the combined DAC and Belinostat treatment, but remained unaffected by Belinostat alone, with the exception of GLUL.…”
Section: Discussionsupporting
confidence: 89%
“…Among those changes, hypermethylation at CGI promoters and associated epigenetic silencing are prevalent in various cell line models (Dai et al, 2008;Li et al, 2009;Chang et al, 2010) and are thought to, either alone or in combination with genetic changes, account for the loss of expression of key genes in the platinum-responsive phenotype. However, our knowledge of whether these DNA methylation changes and aberrantly inactivated genes are actually driving chemoresistance is limited.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…However, it remains puzzling that genomic expression patterns of platinum-sensitive̸-resistant determinants in several cell lines, including squamous cell carcinoma of the head and neck, bladder and ovarian cancers, do not always correlate with the results of biochemical analyses (4)(5)(6). Additionally, epigenetic changes in the DNA methylation profiles during cancer development are associated with the acquisition of cisplatin resistance (6)(7)(8)(9). However, the problem of platinum resistance at the genomic and epigenomic levels has not been clearly defined.…”
Section: Introductionmentioning
confidence: 99%
“…The TFBS and the CGIs targeted for DNA methylation, significantly affect the functional activities of alternative promoters (6)(7)(8)(9)18,19). To date, the role and molecular characteristics of alternative promoters have not been investigated in platinum drug resistance.…”
Section: Introductionmentioning
confidence: 99%