Synthetic lethality of mRNA quality control complexes in cancer.

ABSTRACT: Synthetic lethality exploits the genetic vulnerabilities of cancer cells to enable a targeted, precision approach to treat cancer¹. Over the past 15 years, synthetic lethal cancer target discovery approaches have led to clinical successes of PARP inhibitors² and ushered several next-generation therapeutic targets such as WRN³, USP1⁴, PKMYT1⁵, POLQ⁶ and PRMT5⁷ into the clinic. Here we identify, in human cancer, a novel synthetic lethal interaction between the PELO-HBS1L and SKI complexes of the mRNA quality control pathway. In distinct genetic contexts, including 9p21.3-deleted and high microsatellite instability (MSI-H) tumours, we found that phenotypically destabilized SKI complex leads to dependence on the PELO-

SUBMITTER: Prindle V 

PROVIDER: S-EPMC11864970 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature