Emerging strategies for cancer therapy by ATR inhibitors.

ABSTRACT: DNA replication stress (RS) causes genomic instability and vulnerability in cancer cells. To counteract RS, cells have evolved various mechanisms involving the ATR kinase signaling pathway, which regulates origin firing, cell cycle checkpoints, and fork stabilization to secure the fidelity of replication. However, ATR signaling also alleviates RS to support cell survival by driving RS tolerance, thereby contributing to therapeutic resistance. Cancer cells harboring genetic mutations and other changes that disrupt normal DNA replication increase the risk of DNA damage and the levels of RS, conferring addiction to ATR activity for sustainable replication and susceptibility to therapeutic approaches using ATR inhibitors (ATRis). Therefore, clinical trials are currently being conducted to eval

SUBMITTER: Yano K 

PROVIDER: S-EPMC10323102 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature