A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.

ABSTRACT:

Background

Synthetic lethal interactions are attractive therapeutic candidates as they enable selective targeting of cancer cells in which somatic alterations have disrupted one member of a synthetic lethal gene pair while leaving normal tissues untouched, thus minimising off-target toxicity. Despite this potential, the number of well-established and validated synthetic lethal gene pairs is modest.

Results

We generate a dual-guide CRISPR/Cas9 Library and analyse 472 predicted synthetic lethal pairs in 27 cancer cell Lines from melanoma, pancreatic and lung cancer Lineages. We report a robust collection of 117 genetic interactions within and across cancer types and explore their candidacy as therapeutic targets. We show that SLC25A28 is an attractive target since its syntheti

SUBMITTER: Harle V 

PROVIDER: S-EPMC12445041 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature