Across multiple cancer types, hotspot mutations in SF3B1 confer selective sensitivity to multiple clinically available PARP inhibitors. This sensitivity is due to reduced levels of CINP specifically in SF3B1-mutant cells, which leads to a loss of the canonical replication stress response after challenge with PARP inhibitors.
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This is a summary of: Bland, P. et al. SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response. Nat. Genet. https://doi.org/10.1038/s41588-023-01460-5 (2023).
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SF3B1-mutant cells succumb to replication stress under PARP inhibition. Nat Genet 55, 1265–1266 (2023). https://doi.org/10.1038/s41588-023-01461-4