RAS proto-oncogene GTPase (RAS)

RAS proto-oncogene GTPase refers to a family of related small GTP-binding proteins (HRAS, KRAS, NRAS), functioning as molecular switches in cell signaling. In response to extracellular cues, Ras cycles between an inactive GDP-bound state and an active GTP-bound state, regulated by GEFs and GAPs. Active Ras triggers major signaling cascades (notably the RAF-MEK-ERK and PI3K-AKT pathways) that control cell growth, proliferation, differentiation, and survival. Mutations in Ras genes—especially at residues G12 and Q61—cause constitutive activation, driving malignant transformation and uncontrolled cell division. This makes Ras one of the most important targets in cancer therapy, although direct drugging of Ras has posed major challenges due to its structure and cellular ubiquity. Targeted therapies, particularly for KRAS G12C, have recently shown clinical efficacy, and efforts continue to expand Ras-targeted therapeutics.

Other names

Rat sarcoma proteinSmall GTPaseHRASKRASNRAS

Inhibition of GTP binding or GTPase activity (blocking active/on state) Targeting downstream Ras effectors (e.g., MAPK pathway inhibition) Inhibition of Ras membrane localization (e.g., by blocking prenylation)