title: Mitotic catastrophe and cancer drug resistance: A link that must to be broken.
abstract: An increased tendency of genomic alterations during the life cycle of cells leads to genomic instability, which is a major driving force for tumorigenesis. A considerable fraction of tumor cells are tetraploid or aneuploid, which renders them intrinsically susceptible to mitotic aberrations, and hence, are particularly sensitive to the induction of mitotic catastrophe. Resistance to cell death is also closely linked to genomic instability, as it enables malignant cells to expand even in a stressful environment. Currently it is known that cells can die via multiple mechanisms. Mitotic catastrophe represents a step preceding apoptosis or necrosis, depending on the expression and/or proper function of several proteins. Mitotic catastrophe was proposed to be an onco-suppressive mechanism and the evasion of mitotic catastrophe constitutes one of the gateways to cancer development. Thus, stimulation of mitotic catastrophe appears to be a promising strategy in cancer treatment. Indeed, several chemotherapeutic drugs are currently used at concentrations that induce apoptosis irrespective of the cell cycle phase, yet are very efficient at triggering mitotic catastrophe at lower doses, significantly limiting side effects. In the present review we summarize current data concerning the role of mitotic catastrophe in cancer drug resistance and discuss novel strategies to break this link.
authors.affiliation: Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Denisenko
authors.affiliation: Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Sorokina
authors.affiliation: Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gogvadze
authors.affiliation: Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden. Electronic address: Boris.Zhivotovsky@ki.se.
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D042822:Genomic Instability / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Drug resistance; Genomic instability; Mitotic catastrophe