The CRISPR road: from bench to bedside on an RNA-guided path

The development of next-generation sequencing has greatly expanded our understanding of genomic alterations in cancer. This has furthered a need for new research strategies, particularly the generation of animal models for novel genetic alterations such as insertions, deletions or chromosomal rearrangements. As sequencing technology has increased its efficiency and resolution in recent years, the classic generation of genetically engineered mouse models cannot keep up with the pace of new discoveries. Gene editing in embryonic stem cells using homologous recombination has provided excellent mouse models to study alterations in tumor suppressor genes and oncogenes, however this approach is time-consuming and costly. Another significant limitation to these models is that germline mutations are constitutively present throughout all tissues in the mouse, limiting their relevance to the organ-specific somatic mutations that produce most human cancers. cDNA-based over-expression and RNA interference-mediated knockdown have also allowed scientists to study particular genes or changes in expression of key drivers, but these models are far from physiological. Ideally, a successful model system would overcome these key limitations, and would also be able to adapt quickly to accommodate the plethora of new targets and growing diversity of genomic changes that have been implicated in cancer development.