title: Selective targeting of the G2/M cell cycle checkpoint to improve the therapeutic index of radiotherapy.
abstract: Despite tremendous advances in radiotherapy techniques, allowing dose escalation to tumour tissues and sparing of organs at risk, cure rates from radiotherapy or chemoradiotherapy remain suboptimal for most cancers. In tandem with our growing understanding of tumour biology, we are beginning to appreciate that targeting the molecular response to radiation-induced DNA damage holds great promise for selective tumour radiosensitisation. In particular, approaches that inhibit cell cycle checkpoint controls offer a means of exploiting molecular differences between tumour and normal cells, thereby inducing so-called cancer-specific synthetic lethality. In this overview, we discuss cellular responses to radiation-induced damage and discuss the potential of using G2/M cell cycle checkpoint inhibitors as a means of enhancing tumour control rates.
authors.affiliation: The Institute of Cancer Research, Targeted Therapy Team, Chester Beatty Laboratories, London, UK; The Royal Marsden Hospital, London, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Dillon
authors.affiliation: The Royal Marsden Hospital, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Good
authors.affiliation: The Institute of Cancer Research, Targeted Therapy Team, Chester Beatty Laboratories, London, UK; The Royal Marsden Hospital, London, UK. Electronic address: Kevin.Harrington@icr.ac.uk.
authors.forename: K J
authors.initials: KJ
authors.lastname: Harrington
mesh_terms: D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D059248:Chemoradiotherapy; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011494:Protein Kinases / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*
chemical_list: D011838:Radiation-Sensitizing Agents; D018000:Receptors, Peptide; C070309:anthrax toxin receptors; D004247:DNA; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: ATR inhibition; Chk1 inhibition; checkpoint inhibition; radiosensitisation