CRISPR screen identifies new cancer target

Researchers at Fox Chase Cancer Center, Philadelphia, have used CRISPR-based screening to show that DHX9 potently represses the innate immune response in small cell lung cancer (SCLC) cells through double-stranded RNA (dsRNA) repression.

DHX9 was then depleted in vivo by an inducible system in SCLC cells implanted into mice. Upon induction, dsRNA accumulated and triggered an innate immune response, resulting in a more immunogenic tumour microenvironment. Increased DNA damage and replication stress in SCLCs led to decreased tumour growth.

The research provides a new perspective on treating "cold" tumours like SCLC that typically elicit a weak or non-existent immune response. Targeting DHX9 can make these tumours more responsive to immunotherapies and offers a novel strategy in cancers where traditional therapies have limited effectiveness.

The study was led by Israel Cañadas Castillo and the paper was published yesterday in Cancer Discovery. You can read it here.