Targeted inhibition of the CREB1-CtIP axis enhances the efficacy of abiraterone combined with radiotherapy in prostate cancer - PubMed
4 hours ago
- #DNA repair
- #combination therapy
- #prostate cancer
- Abiraterone acetate (AA) combined with radiotherapy (RT) is used for locally advanced prostate cancer, but not effective for all and may lose sensitivity over time.
- The study finds that Abi (active form) and RT increase CtIP expression, which is linked to poor prognosis and is key in homologous recombination repair (HR) of DNA damage.
- Both Abi and RT enhance CREB1 transcriptional activity via phosphorylation, regulating CtIP expression.
- In prostate cancer development, DNA demethylases (TETs) reduce CtIP promoter methylation, promoting CREB1 binding to the CtIP promoter.
- In vitro and in vivo experiments show that the CREB1 inhibitor 666-15 significantly boosts the efficacy of Abi-RT combination therapy.
- Targeted inhibition of the CREB1-CtIP axis improves treatment outcomes, offering a potential new clinical strategy for prostate cancer.