Loss-of-function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5-fluorouracil and irinotecan treatment in colorectal cancer.

ABSTRACT:

Background

Colorectal cancer (CRC) remains a major global health concern, partly due to resistance to therapy and the lack of new effective treatments for advanced disease. The combination of 5-Fluorouracil (5FU, a thymidylate synthase inhibitor) and irinotecan (a topoisomerase 1 inhibitor) is widely used in first-line and subsequent treatments. This study aimed to identify novel therapeutic targets to enhance combinatorial therapy, improving treatment efficacy and durability of response.

Methods

We performed a loss-of-function screen using HT29 CRC cell line and a retroviral library containing 7296 shRNAs targeting 912 chromatin genes. Cells were then treated with 5FU and SN38 (the active metabolite of irinotecan) or left untreated for 4 weeks. Genes enriched in resistant c

SUBMITTER: Queralt C 

PROVIDER: S-EPMC12741922 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature