KRAS, an abbreviation of Kirsten Rat Sarcoma, is a crucial oncogene involved in cellular proliferation and survival. It belongs to the RAS family, existing in three isoforms (K-RAS, H-RAS, and N-RAS), with KRAS being the most commonly mutated. The Ras protein has GTPase activity, cycling between an inactive (GDP-bound) and active (GTP-bound) form. When activated, it triggers intracellular signaling pathways like the mitogen-activated protein kinase (MAPK) pathway, which is vital for cell proliferation and angiogenesis [5].

KRAS mutations occur in about a quarter of all human cancers [2]. In pancreatic cancer, over 90% of pancreatic ductal adenocarcinomas (PDACs) carry KRAS mutations, mainly G12D, G12V, and G12R, which are key in tumor initiation and progression [3,4]. In colorectal cancer, around half of the cases have KRAS mutations, associated with a worse prognosis [6]. Although KRAS has long been considered undruggable, recent developments include covalent inhibitors targeting KRASG12C, which show promise in early clinical trials for KRASG12C mutant pancreatic cancer [1]. However, most KRAS oncoproteins remain challenging to target, and efforts are ongoing to develop inhibitors for other mutations like the KRAS G12D-directed MRTX1133 inhibitor now in clinical trials [3].

In conclusion, KRAS is a master oncogene with a significant role in the development of various cancers, especially pancreatic and colorectal cancers. The study of KRAS-related mouse models, like gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially help in understanding its function and developing more effective therapeutic strategies against KRAS-mutant cancers.