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Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens1–6. Despite advances in treatment with immune checkpoint inhibitors7–10, there is an unmet need in the treatment of MSI cancers11–14. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy. HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation. Pharmacological inhibition by HRO761 recapitulated the phenotype observed by WRN genetic suppression, leading to DNA damage and inhibition of tumour cell growth selectively in MSI cells in a p53-independent manner. Moreover, HRO761 led to WRN degradation in MSI cells but not in microsatellite-s ....

Protein Data Bank , Cancer Cell Line Encyclopedia , Extended Data , Supplementary Information , Extended Data Table , Horizon Oncosignature , Supplementary Table ,

Universal, essential biomarker identified for childhood neuroblastoma

Researchers have newly identified a universal, essential biomarker for the childhood cancer neuroblastoma – and a potential new target for treatment. ....

San Francisco , United States , Julie Saba , Broad Institute Cancer Cell Line Encyclopedia , University Of California , Broad Institute , Cancer Cell Line Encyclopedia , Dependency Map , Brain Cancer , Cell Line , Ene Expression ,

New Pediatric Cancer Marker Boosts Hope for Treatment

New Pediatric Cancer Marker Boosts Hope for Treatment
miragenews.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from miragenews.com Daily Mail and Mail on Sunday newspapers.

San Francisco , United States , Julie Saba , Edna Beck , Swim Across America Foundation , School Of Medicine , Pediatric Cancer Research , Broad Institute Cancer Cell Line Encyclopedia , University Of California , Goal Foundation , Baldrick Foundation , Broad Institute , Cancer Cell Line Encyclopedia , Dependency Map , Edna Beck Chair ,

New pediatric cancer marker: Hope for a treatment target

New pediatric cancer marker: Hope for a treatment target
medicalxpress.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from medicalxpress.com Daily Mail and Mail on Sunday newspapers.

Julie Saba , Babak Oskouian , Broad Institute Cancer Cell Line Encyclopedia , Broad Institute , Cancer Cell Line Encyclopedia , Dependency Map ,

PTEN status determines chemosensitivity to proteasome inhibition in cholangiocarcinoma

PTEN status determines chemosensitivity to proteasome inhibition in cholangiocarcinoma
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

Proteostat Aggresome , Drug Administration , Celltiter Glo Luminescent Cell Viability , Gene Ontology , Drug Sensitivity , Cancer Therapeutics Response Portal , Cancer Cell Line Encyclopedia ,