Dana-Farber Cancer Institute: Identification of Therapeutic Targets in KRAS Driven Lung Cancer
The CTD2 Center at Dana Farber Cancer Institute focuses on the use of high-throughput genetic and bioinformatic approaches to identify and credential oncogenes and co-dependencies in cancers. This Center aims to provide the cancer research community with information that will facilitate the prioritization of targets based on both genomic and functional evidence, inform the most appropriate genetic context for downstream mechanistic and validation studies, and enable the translation of this information into therapeutics and diagnostics.
The goal of this project is to detect synthetic lethal partners of oncogenic KRAS, using systematic RNAi and CRISPR screening across large numbers of genomically annotated cancer cell lines. For a representative example, they found that the non-canonical IkappaB kinase TBK1 was selectively essential in cells that contain mutant KRAS.
In the case of TBK1, essential genes in human malignant and non-transformed cell lines were identified by performing arrayed format RNA interference (RNAi) screens in 19 cell lines using a short hairpin RNA (shRNA) library targeting kinases, phosphatases and oncogenes.
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If you cannot access the manuscript, or if you have additional questions, please email Joshua Dempster.
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