AI Article Synopsis
- Pancreatic cancer is highly lethal, with about 10% of cases linked to familial pancreatic cancer (FPC) due to genetic mutations affecting DNA repair.
- Researchers created specific pancreatic cancer cell lines lacking certain genes to test drug responses, discovering that these -deficient cells are particularly vulnerable to BET inhibitors.
- The study indicates that using BET inhibition not only triggers increased autophagy but also leads to cell death, proposing it as a potential new treatment for -deficient pancreatic cancer.
Article Abstract
Pancreatic cancer is one of the deadliest diseases in human malignancies. Among total pancreatic cancer patients, ∼10% of patients are categorized as familial pancreatic cancer (FPC) patients, carrying germline mutations of the genes involved in DNA repair pathways ( ). Personalized medicine approaches tailored toward patients' mutations would improve patients' outcome. To identify novel vulnerabilities of -deficient pancreatic cancer, we generated isogenic -deficient murine pancreatic cancer cell lines and performed high-throughput drug screens. High-throughput drug screening revealed that -deficient cells are sensitive to Bromodomain and Extraterminal Motif (BET) inhibitors, suggesting that BET inhibition might be a potential therapeutic approach. We found that deficiency increased autophagic flux, which was further enhanced by BET inhibition in -deficient pancreatic cancer cells, resulting in autophagy-dependent cell death. Our data suggests that BET inhibition can be a novel therapeutic strategy for -deficient pancreatic cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312597 | PMC |
| http://dx.doi.org/10.1101/2023.05.30.542934 | DOI Listing |
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