Cancer cells typically heavily rely on the G2/M checkpoint to survive endogenous and
exogenous DNA damage, such as genotoxic stress due to genome instability or radiation
and chemotherapy. The key regulator of the G2/M checkpoint, the cyclin-dependent kinase 1
(CDK1), is tightly controlled, including by its phosphorylation state. This posttranslational
modification, which is determined by the opposing activities of the phosphatase cdc25 and
the kinase Wee1, allows for a more rapid response to cellular stress than via the synthesis or …

The DNA damage response (DDR) is an elegant system, coordinating DNA repair with cell
cycle checkpoints, that evolved to protect living organisms from the otherwise fatal levels of
DNA damage inflicted by endogenous and environmental sources. Since many agents used
to treat cancer; radiotherapy and cytotoxic chemotherapy, work by damaging DNA the DDR
represents a mechanism of resistance. The original rational for the development of drugs to
inhibit the DDR was to overcome this mechanism of resistance but clinical studies using this …