ATR is a critical dependency gene for uveal melanoma

The oncogene ATR (ATR checkpoint kinase) has been identified as a critical dependency gene for uveal melanoma (UM) cells. Researchers used the Dependency Map (DepMap) to discover that inhibiting ATR with the selective inhibitor VE-822 affected three UM cell models with varying risk levels. This inhibition led to DNA double-strand break formation, micronuclei accumulation, and a reduction in colony and spheroid formation.

RNA sequencing and pathway enrichment analysis suggest that successful completion of S phase and mitotic progression are crucial for UM cells' response to ATR inhibition. The authors further support their hypothesis by combining ATR and microtubule inhibition, which showed significant synergy in the UM models. The findings highlight ATR as a potential therapeutic vulnerability in uveal melanoma, providing insight into the gene's role in tumor cell proliferation and survival.