title: Targeting the Checkpoint to Kill Cancer Cells.
abstract: Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells.
authors: Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ14200 Prague, Czech Republic. jan.benada@img.cas.cz.|Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, CZ12844 Prague, Czech Republic. jan.benada@img.cas.cz.
authors: Jan
authors: J
authors: Benada
authors: Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ14200 Prague, Czech Republic. libor.macurek@img.cas.cz.
authors: Libor
authors: L
authors: Macurek
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53
keywords: ATM; ATR; Chk1; DNA damage response; Wee1; cancer; checkpoint; inhibitor; p53; replication stress