Chromatin Stability as a Target for Cancer Treatment.
DNA damage
DNA-binding small molecules
anti-cancer treatment
chromatin damage
Journal
BioEssays : news and reviews in molecular, cellular and developmental biology
ISSN: 1521-1878
Titre abrégé: Bioessays
Pays: United States
ID NLM: 8510851
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
08
08
2018
revised:
29
10
2018
entrez:
20
12
2018
pubmed:
20
12
2018
medline:
28
7
2019
Statut:
ppublish
Résumé
In this essay, I propose that DNA-binding anti-cancer drugs work more via chromatin disruption than DNA damage. Success of long-awaited drugs targeting cancer-specific drivers is limited by the heterogeneity of tumors. Therefore, chemotherapy acting via universal targets (e.g., DNA) is still the mainstream treatment for cancer. Nevertheless, the problem with targeting DNA is insufficient efficacy due to high toxicity. I propose that this problem stems from the presumption that DNA damage is critical for the anti-cancer activity of these drugs. DNA in cells exists as chromatin, and many DNA-targeting drugs alter chromatin structure by destabilizing nucleosomes and inducing histone eviction from chromatin. This effect has been largely ignored because DNA damage is seen as the major reason for anti-cancer activity. I discuss how DNA-binding molecules destabilize chromatin, why this effect is more toxic to tumoral than normal cells, and why cells die as a result of chromatin destabilization.
Identifiants
pubmed: 30566250
doi: 10.1002/bies.201800141
pmc: PMC6522245
mid: NIHMS1018136
doi:
Substances chimiques
Antineoplastic Agents
0
Chromatin
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Pagination
e1800141Subventions
Organisme : NCI NIH HHS
ID : R01 CA197967
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA198395
Pays : United States
Organisme : NIH HHS
ID : RO1CA197967
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 The Authors. BioEssays Published by Wiley Periodicals, Inc.
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