The Rat Sarcoma (ras) proto-oncogenes are the first human oncogenes to be discovered[2], encoding for KRAS, NRAS, and HRAS. Ras proteins belongs to small GTPase superfamily, that can hydrolyze GTP to GDP. This hydroxylation ability is key to transmit the signals to the downstream pathways. In neural state, Ras proteins binds GDP. When the molecular signal passes through Ras proteins, the bounded GDP is expelled by guanine nucleotide exchange factors, allowing for GTP binding[2], and thereby "switching on" Ras proteins to drive cell growth, differentiation, and survival via AKT and ERK pathways, Normally, the bound GTP is fairly hydrolyzed to GDP, "switching off" Ras proteins. By mutations, Ras proteins lose the ability to switch on and off, are locked in the active ("on") state, become oncogenes. Different cancers favor different ras genes (e.g., KRAS in pancreas/colon/lung, NRAS in melanoma, HRAS in bladder).

[1] G. Klein and E. Klein, “Oncogene activation and tumor progression,” Carcinogenesis, vol. 5, no. 4, pp. 429–435, 1984, doi: 10.1093/carcin/5.4.429.

[2] D. S. Goodsell, “The Molecular Perspective: The ras Oncogene,” The Oncologist, vol. 4, no. 3, pp. 263–264, June 1999, doi: 10.1634/theoncologist.4-3-263.