title: Doxorubicin, DNA torsion, and chromatin dynamics.
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.
authors.affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Sheila S
authors.initials: SS
authors.lastname: Teves
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: cjkemp@fhcrc.org.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kemp
authors.affiliation: 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.
authors.forename: Steven
authors.initials: S
authors.lastname: Henikoff
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002843:Chromatin / Q000187:drug effects*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D009707:Nucleosomes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D009707:Nucleosomes; D004317:Doxorubicin; D004247:DNA
keywords: Anthracycline; Cancer; Chemotherapy; Chromatin dynamics; DNA torsion; Doxorubicin