Focusing on NSCLC, it has been possible to rapidly generate three genetically distinct tumor models, by specific modification of KrasG12D and KrasG12C, in conjunction with either Trp53 or Stk11. Each of the models generated tumors with a latency of 4–12 weeks and within the course of tumor experiments, health status of the animal was only impacted by disease burden and not by nonspecific side effects of the Cas9 system. The gene discussed is TP53; the disease is non-small cell lung carcinoma.