Abrogation of the G2/M checkpoint as a chemosensitization approach for alkylating agents.

ABSTRACT:

Background

The cell cycle is tightly regulated by checkpoints, which play a vital role in controlling its progression and timing. Cancer cells exploit the G2/M checkpoint, which serves as a resistance mechanism against genotoxic anticancer treatments, allowing for DNA repair prior to cell division. Manipulating cell cycle timing has emerged as a potential strategy to augment the effectiveness of DNA damage-based therapies.

Methods

In this study, we conducted a forward genome-wide CRISPR/Cas9 screening with repeated exposure to the alkylating agent temozolomide (TMZ) to investigate the mechanisms underlying tumor cell survival under genotoxic stress.

Results

Our findings revealed that canonical DNA repair pathways, including the Ataxia-telangiectasia mutated (ATM)/Fanc

SUBMITTER: Lang F 

PROVIDER: S-EPMC11145461 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature