Replication stress in cancer: origins, consequences and therapeutic opportunities.

Replication stress drives tumor evolution and creates therapeutic vulnerabilities, with over 100 clinical trials exploring ATR, CHK1, and WEE1 inhibitors.

• Why it matters: Understanding how replication stress contributes to genomic instability is crucial for developing targeted cancer therapies and overcoming resistance.
• What they did: The authors review molecular mechanisms of replication stress, its role in cancer progression, and strategies like synthetic lethality, including PARP and WRN inhibition, to exploit these vulnerabilities.
• The result: Targeting replication stress response pathways offers promising avenues for precision oncology, enabling treatments tailored to tumor-specific dependencies and reducing genomic instability.