title: The DNA damage-induced cell death response: a roadmap to kill cancer cells.
abstract: Upon massive DNA damage cells fail to undergo productive DNA repair and trigger the cell death response. Resistance to cell death is linked to cellular transformation and carcinogenesis as well as radio- and chemoresistance, making the underlying signaling pathways a promising target for therapeutic intervention. Diverse DNA damage-induced cell death pathways are operative in mammalian cells and finally culminate in the induction of programmed cell death via activation of apoptosis or necroptosis. These signaling routes affect nuclear, mitochondria- and plasma membrane-associated key molecules to activate the apoptotic or necroptotic response. In this review, we highlight the main signaling pathways, molecular players and mechanisms guiding the DNA damage-induced cell death response.
authors.affiliation: German Cancer Research Center (dkfz), Cellular Senescence Group, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Matt
authors.affiliation: German Cancer Research Center (dkfz), Cellular Senescence Group, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. t.hofmann@dkfz.de.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
mesh_terms: D000375:Aging; D000818:Animals; D016923:Cell Death; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
keywords: ATM; ATR; Adriamycin; Axin; BAX; Cancer therapy; Caspase 2; Chk1; Chk2; Doxorubicin; FOXO3; HIPK2; Hippo pathway; Ionizing radiation; MLKL; PIDD; PML; PUMA; Pin1; RIPK1; RIPK3; SUMO; XAF1; Yap1; c-Abl; p53; p53 Serine 46; p73