title: Genotoxic anti-cancer agents and their relationship to DNA damage, mitosis, and checkpoint adaptation in proliferating cancer cells.
abstract: When a human cell detects damaged DNA, it initiates the DNA damage response (DDR) that permits it to repair the damage and avoid transmitting it to daughter cells. Despite this response, changes to the genome occur and some cells, such as proliferating cancer cells, are prone to genome instability. The cellular processes that lead to genomic changes after a genotoxic event are not well understood. Our research focuses on the relationship between genotoxic cancer drugs and checkpoint adaptation, which is the process of mitosis with damaged DNA. We examine the types of DNA damage induced by widely used cancer drugs and describe their effects upon proliferating cancer cells. There is evidence that cell death caused by genotoxic cancer drugs in some cases includes exiting a DNA damage cell cycle arrest and entry into mitosis. Furthermore, some cells are able to survive this process at a time when the genome is most susceptible to change or rearrangement. Checkpoint adaptation is poorly characterised in human cells; we predict that increasing our understanding of this pathway may help to understand genomic instability in cancer cells and provide insight into methods to improve the efficacy of current cancer therapies.
authors.affiliation: Cancer Cell Laboratory, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. l.swift@uleth.ca.
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Swift
authors.affiliation: Cancer Cell Laboratory, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. roy.golsteyn@uleth.ca.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Golsteyn
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000187:drug effects* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents