PTEN and neoplasm: The most relevant example is the use of pre-existing Cre/LoxP-based genetically modified mouse models (GEMMs) to activate the oncogene KRasG12D and delete the tumor suppressor Trp53 and subsequently, knock out additional tumor suppressors like Nkx2.1, Pten and Apc using the CRISPR/Cas9 system [75].