Preclinical: LIG1 as possible target for PARP inhibitors

[Maxone73]

I write about this preclinical study with pleasure, as one of the researchers is a friend.

A recent pre-print study from December 24, 2024, explores new ways to treat castration-resistant prostate cancer (CRPC) by targeting DNA repair genes (DRG) beyond HRR genes.

The study found, using CRISPR/Cas9, that losses of LIG1, EME1, and FAAP24 act as PARPi sensitizers. Inactivating LIG1 and PARP together causes a synthetic lethality (SL) effect, leading to cell death. This SL effect was also observed in lung, breast, and colorectal cancers, suggesting a broad therapeutic potential.

The research suggests that determining LIG1 status is important for stratifying CRPC patients and expanding their treatment options.

My take on this is that if we have (or develop) a LIG1 inhibitor, it could be used together with a PARPi to hit the bastard!

prostatewarriors.com/2024/1...