MYC predetermines the sensitivity of gastrointestinal cancer to antifolate drugs through regulating TYMS transcription.

ABSTRACT: BACKGROUND:Thymidylate synthase (TYMS) is a successful chemotherapeutic target for anticancer therapy. Numerous TYMS inhibitors have been developed and used for treating gastrointestinal cancer now, but they have limited clinical benefits due to the prevalent unresponsiveness and toxicity. It is urgent to identify a predictive biomarker to guide the precise clinical use of TYMS inhibitors. METHODS:Genome-scale CRISPR-Cas9 knockout screening was performed to identify potential therapeutic targets for treating gastrointestinal tumours as well as key regulators of raltitrexed (RTX) sensitivity. Cell-based functional assays were used to investigate how MYC regulates TYMS transcription. Cancer patient data were used to verify the correlation between drug response and MYC and/or TYMS mRNA levels

SUBMITTER: Liu T 

PROVIDER: S-EPMC6838448 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature