ARID1A loss sensitizes colorectal cancer cells to floxuridine.

ABSTRACT: The loss-of-function mutation of AT-rich interactive domain 1A (ARID1A) frequently occurs in various types of cancer, making it a promising therapeutic target. In the present study, we performed a screening of an FDA-approved drug library in ARID1A isogenic colorectal cancer (CRC) cells and discovered that ARID1A loss sensitizes CRC cells to floxuridine (FUDR), an antineoplastic agent used for treating hepatic metastases from CRC, both in vivo and in vitro. As a pyrimidine analogue, FUDR induces DNA damage by inhibiting thymidylate synthase (TS) activity. ARID1A, as a regulator of DNA damage repair, when lost, exacerbates FUDR-induced DNA damage, leading to increased cell apoptosis. Specifically, ARID1A deficiency impairs DNA damage repair by downregulating Chk2 phosphorylation, thereby se

SUBMITTER: Xiang C 

PROVIDER: S-EPMC11531615 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature