RAS pathway protein (RAS)

The RAS pathway proteins are a family of small GTPases that act as central molecular switches in the control of cell proliferation, differentiation, and survival[1][2][4]. The three main RAS isoforms (KRAS, NRAS, HRAS) cycle between inactive GDP-bound and active GTP-bound states, relaying growth signals from cell surface receptors to multiple downstream effector pathways, most notably the RAF-MEK-ERK (MAPK) and PI3K-AKT pathways[3][4]. Activating mutations in RAS genes are among the most common oncogenic events in human cancer, making these proteins major therapeutic targets; however, direct targeting has only recently become feasible with the advent of mutant-specific covalent inhibitors (e.g., sotorasib for KRAS G12C)[2][4][6]. Indirect approaches targeting downstream effectors remain an important strategy. RAS signaling is also implicated in developmental syndromes and certain inflammatory and degenerative diseases[1]. The complexity and redundancy of RAS pathway signaling, together with normal tissue dependence, present ongoing challenges for therapeutic targeting.

Other names

RAS proteinsRat sarcoma proteinsRAS familyKRAS, NRAS, HRAS (for the three main human isoforms)

Covalent inhibition of mutant KRAS G12C (e.g., sotorasib, adagrasib); Inhibition of downstream signaling pathways (RAF, MEK, PI3K, mTOR); Disruption of nucleotide exchange or effector interactions (experimental); RNA interference (siRNA for KRAS knockdown); Allosteric inhibition (emerging research)