Exposing cancer with CRISPR-Cas9: from genetic identification to clinical therapy

Abstract

: Cancer genomes commonly harbor many genetic aberrations which are often associated with carcinogenesis, progression, metastasis and tolerance. The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9), has been extensively utilized as a precise genome editing tool for genetic screens of cancer. Comprehensive CRISPR-Cas9 libraries and databases have been established for cancer researches, and some essential genes, druggable targets or biomarkers have been identified by CRISPR-Cas9 technology. The identified genes that are helpful to uncover genotype-phenotype interactions by establishing cell or animal models with gene knockout or knock-in, and the druggable targets or biomarkers provide an approach to cancer treatment or diagnosis. Furthermore, combined with pharmaceutical delivery system, CRISPR-Cas9 system has been directly applied for cancer gene therapy and some exciting results have been reported from different research groups. Furthermore, immune cells edited with the CRISPR-Cas9 system have been developed for cancer immunotherapies, 11 of which have entered phase I/II stage clinical trials up to now. This review focused on the application of the CRISPR-Cas9 system for cancer research, including oncogene identification, genetic screen, druggable targets, cell or animal models, gene therapy, cell therapy, and clinical trials. In addition, some concerns about translational CRISPR-Cas9 therapeutics are also addressed for cancer therapy. Altogether, the CRISPR-Cas9 system is a powerful tool for cancer research and a promising approach to cancer therapy.