CRISPR screen in cancer: status quo and future perspectives

Clustered regularly interspaced short palindromic repeats (CRISPR) system offers a powerful platform for genome manipulation, including protein-coding genes, noncoding RNAs and regulatory elements. The development of CRISPR screen enables high-throughput interrogation of gene functions in diverse tumor biologies, such as tumor growth, metastasis, synthetic lethal interactions, therapeutic resistance and immunotherapy response, which are mostly performed in vitro or in transplant models. Recently, direct in vivo CRISPR screens have been developed to identify drivers of tumorigenesis in native microenvironment. Key parameters of CRISPR screen are constantly being optimized to achieve higher targeting efficiency and lower off-target effect. Here, we review the recent advances of CRISPR screen in cancer studies both in vitro and in vivo, with a particular focus on identifying cancer immunotherapy targets, and propose optimizing strategies and future perspectives for CRISPR screen.