Exploiting replicative stress in gynecological cancers as a therapeutic strategy.

ABSTRACT: Elevated levels of replicative stress in gynecological cancers arising from uncontrolled oncogenic activation, loss of key tumor suppressors, and frequent defects in the DNA repair machinery are an intrinsic vulnerability for therapeutic exploitation. The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell de

SUBMITTER: Ngoi NY 

PROVIDER: S-EPMC7418601 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature