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Chemical genetic screening of KRAS-based synthetic lethal inhibitors for pancreatic cancer.
- Source :
-
Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2009 Jan 01; Vol. 14 (8), pp. 2904-10. Date of Electronic Publication: 2009 Jan 01. - Publication Year :
- 2009
-
Abstract
- Pancreatic cancer is one of the deadliest diseases largely due to difficulty in early diagnosis and the lack of effective treatments. KRAS is mutated in more than 90% of pancreatic cancer patients, and oncogenic KRAS contributes to pancreatic cancer tumorigenesis and progression. In this report, using an oncogenic KRASV12-based pancreatic cancer cell model, we developed a chemical genetic screen to identify small chemical inhibitors that selectively target pancreatic cancer cells with gain-of-function KRAS mutation. After screening ~3,200 compounds, we identified one compound that showed selective synthetic lethality against the KRASV12 transformed human pancreatic ductal epithelial cell over its isogenic parental cell line. These selective KRASV12-synthetic lethal compounds may serve as leads for subsequent development of clinically-effective treatments for pancreatic cancer.
Details
- Language :
- English
- ISSN :
- 2768-6698
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Frontiers in bioscience (Landmark edition)
- Publication Type :
- Academic Journal
- Accession number :
- 19273243
- Full Text :
- https://doi.org/10.2741/3421