RAS

RAS refers to a family of small, membrane-associated guanosine triphosphatases (GTPases) that function as molecular switches in intracellular signal transduction. The principal human RAS proteins are encoded by KRAS, NRAS, and HRAS. They alternate between an inactive GDP-bound state and an active GTP-bound state. Activation is promoted by guanine-nucleotide exchange factors, whereas GTPase-activating proteins accelerate conversion back to the GDP-bound state. Active RAS engages downstream effectors, including RAF kinases such as BRAF, the MAPK cascade involving MEK and MAPK1, and Signaling networks involving PI3K/AKT and Protein kinase B (PKB).

RAS Signaling regulates proliferation, survival, differentiation, migration, and other cellular processes. Activating mutations that impair GTP hydrolysis or otherwise stabilize the GTP-bound state can produce persistent Signaling and contribute to Cancer development. RAS alterations are especially important in pancreatic, colorectal, lung, melanoma, and other Cancers. Therapeutic strategies include inhibitors directed against particular mutant RAS proteins, compounds that bind the active “RAS(ON)” state, and agents that interfere with RAS-dependent Signaling or downstream pathways. RAS activity can also interact functionally with receptors such as the EGFR, with pathway regulators such as PTPN1, and with parallel survival and stress responses involving cytokines, oxidative stress, and apoptotic processes.