Kirsten Ras oncogene: significance of its discovery in human cancer research

The KRAS/ K-RAS oncogene is crucially involved in human cancer. The term "oncogene" -- i.e., a gene able to transform a normal cell into a tumor cell - was introduced in 1969, but the word was not used in the human carcinogenesis literature until much later. Transforming Kras and Hras oncogenes from the Kirsten and Harvey sarcoma viruses were not identified until the early 1980s due to the complicated structures of the viral genomes. Orthologs of these viral oncogenes were then found in transforming DNA fragments in human cancers in the form of mutated versions of the HRAS and KRAS proto-oncogenes. Thus, RAS genes were the first human oncogenes to be identified. Subsequent studies showed that mutated KRAS acted as an in vivo oncogenic driver, as indicated by studies of anti-EGFR therapy for metastatic colorectal cancers. This review addresses the historical background and experimental studies that led to the discovery of Kirsten Ras as an oncogene, the role of mutated KRAS in human carcinogenesis, and recent therapeutic studies of cancer cells with KRAS mutations.