Histone and DNA Methylation as Epigenetic Regulators of DNA Damage Repair in Gastric Cancer and Emerging Therapeutic Opportunities
Gastric cancer (GC), one of the most common malignancies worldwide, is a heterogeneous disease developing from the accumulation of genetic and epigenetic changes. One of the most critical epigenetic alterations in GC is DNA and histone methylation, which affects multiple processes in the cell nucleus, including gene expression and DNA damage repair (DDR). Indeed, the aberrant expression of histone methyltransferases and demethylases influences chromatin accessibility to the DNA repair machinery; moreover, overexpression of DNA methyltransferases results in promoter hypermethylation, which can suppress the transcription of genes involved in DNA repair. Several DDR mechanisms have been recognized so far, with homologous recombination (HR) being the main pathway involved in the repair of double-strand breaks. An increasing number of defective HR genes are emerging in GC, resulting in the identification of important determinants of therapeutic response to DDR inhibitors. This review describes how both histone and DNA methylation affect DDR in the context of GC and discusses how alterations in DDR can help identify new molecular targets to devise more effective therapeutic strategies for GC, with a particular focus on HR-deficient tumors.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
---|---|
Enthalten in: |
Cancers - 15(2023), 20 vom: 13. Okt. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
De Marco, Katia [VerfasserIn] |
---|
Links: |
---|
Themen: |
DNA damage repair |
---|
Anmerkungen: |
Date Revised 30.10.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.3390/cancers15204976 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM363863605 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM363863605 | ||
003 | DE-627 | ||
005 | 20231226094237.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/cancers15204976 |2 doi | |
028 | 5 | 2 | |a pubmed24n1212.xml |
035 | |a (DE-627)NLM363863605 | ||
035 | |a (NLM)37894343 | ||
035 | |a (PII)4976 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a De Marco, Katia |e verfasserin |4 aut | |
245 | 1 | 0 | |a Histone and DNA Methylation as Epigenetic Regulators of DNA Damage Repair in Gastric Cancer and Emerging Therapeutic Opportunities |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 30.10.2023 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a Gastric cancer (GC), one of the most common malignancies worldwide, is a heterogeneous disease developing from the accumulation of genetic and epigenetic changes. One of the most critical epigenetic alterations in GC is DNA and histone methylation, which affects multiple processes in the cell nucleus, including gene expression and DNA damage repair (DDR). Indeed, the aberrant expression of histone methyltransferases and demethylases influences chromatin accessibility to the DNA repair machinery; moreover, overexpression of DNA methyltransferases results in promoter hypermethylation, which can suppress the transcription of genes involved in DNA repair. Several DDR mechanisms have been recognized so far, with homologous recombination (HR) being the main pathway involved in the repair of double-strand breaks. An increasing number of defective HR genes are emerging in GC, resulting in the identification of important determinants of therapeutic response to DDR inhibitors. This review describes how both histone and DNA methylation affect DDR in the context of GC and discusses how alterations in DDR can help identify new molecular targets to devise more effective therapeutic strategies for GC, with a particular focus on HR-deficient tumors | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Review | |
650 | 4 | |a DNA damage repair | |
650 | 4 | |a PARP inhibitors | |
650 | 4 | |a epigenetic alterations | |
650 | 4 | |a gastric cancer | |
650 | 4 | |a histone methyltransferases | |
650 | 4 | |a homologous recombination deficiency | |
650 | 4 | |a methylation | |
700 | 1 | |a Sanese, Paola |e verfasserin |4 aut | |
700 | 1 | |a Simone, Cristiano |e verfasserin |4 aut | |
700 | 1 | |a Grossi, Valentina |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cancers |d 2009 |g 15(2023), 20 vom: 13. Okt. |w (DE-627)NLM198667213 |x 2072-6694 |7 nnns |
773 | 1 | 8 | |g volume:15 |g year:2023 |g number:20 |g day:13 |g month:10 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/cancers15204976 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 15 |j 2023 |e 20 |b 13 |c 10 |