A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer
© 2023. The Author(s)..
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cell death & disease - 14(2023), 9 vom: 21. Sept., Seite 620 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, EunJung [VerfasserIn] |
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| Links: |
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| Themen: |
BRCA2 Protein |
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| Anmerkungen: |
Date Completed 27.09.2023 Date Revised 25.04.2024 published: Electronic UpdateOf: bioRxiv. 2023 May 31;:. - PMID 37398312 Citation Status MEDLINE |
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| doi: |
10.1038/s41419-023-06145-9 |
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| funding: |
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| PPN (Katalog-ID): |
NLM362321116 |
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| 245 | 1 | 2 | |a A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer |
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| 500 | |a published: Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2023 May 31;:. - PMID 37398312 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Fernandez-Vega, Virneliz |e verfasserin |4 aut | |
| 700 | 1 | |a Gangaraju, Ritika |e verfasserin |4 aut | |
| 700 | 1 | |a Beesabathuni, Nitin Sai |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Martin Jean |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Priya S |e verfasserin |4 aut | |
| 700 | 1 | |a Scampavia, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Spicer, Timothy P |e verfasserin |4 aut | |
| 700 | 1 | |a Hwang, Chang-Il |e verfasserin |4 aut | |
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