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Association details:
Biomarker:ATR mutation
Cancer:Colorectal Cancer
Drug:SNB-101 (DNA topoisomerase inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: D – Preclinical
Source:
Title:

A clinically relevant heterozygous ATR mutation sensitizes colorectal cancer cells to replication stress

Published date:
03/31/2022
Excerpt:
We showed that the ATR mutation increases cell sensitivity to several molecules. Amongst them, SN-38 (active metabolite of Irinotecan, topoisomerase I inhibitor) and VE-822 (ATR inhibitor) were those that showed the most dramatic sensitization of ATR mutant cells. The combination of both molecules resulted in highly synergistic effects, reaching a maximum of 50%...Altogether, these results highlight the cytotoxic sensitization of ATR mutant cells to topoisomerase I and ATR inhibitors, either used separately or combined. The combined (SN-38 + VE-822) treatment greatly enhanced apoptosis induction, especially in ATR mutant cells.
DOI:
10.1038/s41598-022-09308-4