Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy

The advent of next-generation sequencing (NGS) and single-cell profiling technologies has revealed the complex and heterogenous ecosystem of human tumors under steady-state and therapeutic perturbation. Breakthroughs in the development of genetically engineered mouse models (GEMM) of human cancers that are based on the combination of two site-specific recombinase systems [dual-recombinase system (DRS)] offer fundamental new possibilities to elucidate and understand critical drivers of the diverse tumor phenotypes and validate potential targets for therapy. Here, we discuss opportunities DRS-based cancer GEMMs offer to model, trace, manipulate, and functionally investigate established cancers, their interactions with the host, and their response to therapy.