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- W3094420004 abstract "Significance Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers to treat. Existing drugs rarely work as a single agent. Therefore, identifying novel drug combinations that will synergistically and selectively kill PDAC cells is a significant unmet need. Here, we used CRISPR gene knockout s creening to identify combinatorial targets of gemcitabine (Gem) in PDAC. We discovered that PRMT5 depletion makes PDAC cells significantly sensitive to Gem. Our mechanistic findings show that PRMT5 inhibition impairs DNA repair mechanism. Hence the combination results in synergistic accumulation of Gem-induced DNA damage. We show that the combination leads to synergistic cell death in PDAC cells in vitro and in vivo." @default.
- W3094420004 created "2020-10-29" @default.
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- W3094420004 date "2020-10-23" @default.
- W3094420004 modified "2023-10-17" @default.
- W3094420004 title "Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells" @default.
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- W3094420004 doi "https://doi.org/10.1073/pnas.2009899117" @default.
- W3094420004 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7668168" @default.
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