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Biochim Biophys Acta. 2014 Jan;1845(1):84-9. doi: 10.1016/j.bbcan.2013.12.002. Epub 2013 Dec 19.

Doxorubicin, DNA torsion, and chromatin dynamics.

Author information

1
Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: cjkemp@fhcrc.org.
3
Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address: steveh@fhcrc.org.

Abstract

Doxorubicin is one of the most important anti-cancer chemotherapeutic drugs, being widely used for the treatment of solid tumors and acute leukemias. The action of doxorubicin and other anthracycline drugs has been intensively investigated during the last several decades, but the mechanisms that have been proposed for cell killing remain disparate and controversial. In this review, we examine the proposed models for doxorubicin action from the perspective of the chromatin landscape, which is altered in many types of cancer due to recurrent mutations in chromatin modifiers. We highlight recent evidence for effects of anthracyclines on DNA torsion and chromatin dynamics that may underlie basic mechanisms of doxorubicin-mediated cell death and suggest new therapeutic strategies for cancer treatment.

KEYWORDS:

Anthracycline; Cancer; Chemotherapy; Chromatin dynamics; DNA torsion; Doxorubicin

PMID:
24361676
PMCID:
PMC3927826
DOI:
10.1016/j.bbcan.2013.12.002
[Indexed for MEDLINE]
Free PMC Article

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