Synthetic-Lethality Screening with PARP1 inhibition

PARP1 plays a central role in DNA repair and is a well-established target across multiple cancer types. Understanding the vulnerabilities associated with PARP1 biology, together with advances in targeted protein degradation and molecular-glue discovery, may help uncover new therapeutic opportunities.

At AACR 2026, WuXi Biology and Testing scientists highlighted complementary approaches spanning whole-genome synthetic-lethality screening, molecular-glue-focused high-throughput screening, and proximity-labeling technologies.

The work presented in this poster applies in vitro and in vivo screening in liver cancer models to identify potential genes that are co-lethal with PARP1 loss or inhibition. It also explores the discovery of CRBN-dependent and CRBN-independent degrader hits, together with a proximity-labeling and proteomics strategy to support candidate E3-ligase identification and prioritization.