Interconnection between DNA damage, senescence, inflammation, and cancer.
In order to deal with endogenous and exogenous factors, including radiation or pathogens, cells evolved different strategies. This includes highly complex processes such as DNA damage response, senescence, cell death, and inflammatory reactions. Recent research indicates an interconnection between the mentioned cellular pathways whilst all of them seem to play a role in induction and progression, but also the prevention of cancerous diseases and therefore qualify for potential prevention and treatment strategies. On the basis of their pivotal functions in cancer biology in general, each of the cellular processes represents promising single therapeutic targets. Further, due to their strong interconnection, targeting all of them in a multimodal approach could be another promising strategy to treat cancer. We, therefore, review the mechanisms of DNA damage induction, detection and repair as well as the induction of cell death. Further, features of senescence and mechanism of inflammation induction and abrogation are outlined. A special focus is set on how senescence and inflammation are related to diseases and how targeting them could contribute to improvement of cancer therapies.
Research Unit, Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1,85764Neuherberg, Germany.
Roland
R
Wunderlich
Department of Radiation Oncology, Universitatsklinikum Erlangen, Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Erlangen, Germany.
Paul-Friedrich
PF
Ruehle
Department of Radiation Oncology, Universitatsklinikum Erlangen, Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Erlangen, Germany.
Lisa
L
Deloch
Research Unit, Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1,85764Neuherberg, Germany.
Kristian
K
Unger
Research Unit, Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1,85764Neuherberg, Germany.
Julia
J
Hess
Research Unit, Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1,85764Neuherberg, Germany.
Horst
H
Zitzelsberger
Department of Radiation Oncology, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
Kirsten
K
Lauber
Department of Radiation Oncology, Universitatsklinikum Erlangen, Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Erlangen, Germany.
Benjamin
B
Frey
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, udo.gaipl@uk-erlangen.de.
Udo S
US
Gaipl
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D016922:Cellular Senescence; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000628:therapy; D009369:Neoplasms / Q000209:etiology* / Q000628:therapy