title: DNA replication stress and cancer: cause or cure?
abstract: There is an extensive and growing body of evidence that DNA replication stress is a major driver in the development and progression of many cancers, and that these cancers rely heavily on replication stress response pathways for their continued proliferation. This raises the possibility that the pathways that ordinarily protect cells from the accumulation of cancer-causing mutations may actually prove to be effective therapeutic targets for a wide range of malignancies. In this review, we explore the mechanisms by which sustained proliferation can lead to replication stress and genome instability, and discuss how the pattern of mutations observed in human cancers is supportive of this oncogene-induced replication stress model. Finally, we go on to consider the implications of replication stress both as a prognostic indicator and, more encouragingly, as a potential target in cancer treatment.
authors.affiliation: Lancaster Medical School, Faculty of Health & Medicine, Lancaster University, Lancaster, LA1 4YG, UK.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Taylor
authors.affiliation: Lancaster Medical School, Faculty of Health & Medicine, Lancaster University, Lancaster, LA1 4YG, UK.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D018450:Disease Progression; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009857:Oncogenes; D015398:Signal Transduction
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATR; CHK1; genome instability; oncogenes; replication stress