Bibliographic Details
| Title: |
A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer |
| Authors: |
EunJung Lee, Suyakarn Archasappawat, Keely Ji, Jocelyn Pena, Virneliz Fernandez-Vega, Ritika Gangaraju, Nitin Sai Beesabathuni, Martin Jean Kim, Qi Tian, Priya S. Shah, Louis Scampavia, Timothy P. Spicer, Chang-Il Hwang |
| Source: |
Cell Death and Disease, Vol 14, Iss 9, Pp 1-11 (2023) |
| Publisher Information: |
Nature Publishing Group, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
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 (e.g., BRCA2). Personalized medicine approaches tailored toward patients’ mutations would improve patients’ outcome. To identify novel vulnerabilities of BRCA2-deficient pancreatic cancer, we generated isogenic Brca2-deficient murine pancreatic cancer cell lines and performed high-throughput drug screens. High-throughput drug screening revealed that Brca2-deficient cells are sensitive to Bromodomain and Extraterminal Motif (BET) inhibitors, suggesting that BET inhibition might be a potential therapeutic approach. We found that BRCA2 deficiency increased autophagic flux, which was further enhanced by BET inhibition in Brca2-deficient pancreatic cancer cells, resulting in autophagy-dependent cell death. Our data suggests that BET inhibition can be a novel therapeutic strategy for BRCA2-deficient pancreatic cancer. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-023-06145-9 |
| Access URL: |
https://doaj.org/article/9724ab7f7f6f42e8a12f619770e9bc57 |
| Accession Number: |
edsdoj.9724ab7f7f6f42e8a12f619770e9bc57 |
| Database: |
Directory of Open Access Journals |
