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