Targeting the Checkpoint to Kill Cancer Cells

Biomolecules

Jan Benada²  Libor Macurek²  Wolf-Dietrich Heyer¹  Thomas Helleday¹ 

[1] Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ14200 Prague, Czech Republic; E-Mail;Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ14200 Prague, Czech Republic; E-Mail:

关键词: checkpoint;    DNA damage response;    replication stress;    cancer;    inhibitor;    ATM;    ATR;    Chk1;    Wee1;    p53;   

DOI  :  10.3390/biom5031912

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.