Neuroblastoma RAS viral oncogene homolog (NRAS), mutated forms (NRAS)

Mutated NRAS refers to oncogenic, constitutively active variants of the small GTPase NRAS, a member of the Ras family encoded by the neuroblastoma RAS viral oncogene homolog gene.[3][5][6] NRAS normally functions as a molecular switch cycling between inactive GDP‑bound and active GTP‑bound states to transmit signals from activated cell‑surface receptors to downstream pathways such as RAF–MEK–ERK and PI3K–AKT, thereby regulating cell proliferation, differentiation, and survival.[3][5][6] Somatic point mutations, most commonly at codons 61 (predominant hotspot), 12, and 13, impair intrinsic and/or GAP‑mediated GTP hydrolysis, locking NRAS in a GTP‑bound “on” state that drives persistent downstream signaling and oncogenic transformation.[3][6][7] NRAS mutations are especially common in melanoma, various hematologic malignancies, and some solid tumors, where mutant NRAS can strongly activate BRAF and other effectors, promoting uncontrolled cell growth and survival.[2][3][7] Because NRAS itself has proven difficult to target directly, current therapeutic approaches for “mutated NRAS”–driven cancers focus on inhibiting downstream effectors (particularly MEK) or parallel signaling pathways, and NRAS mutation status is used as a molecular biomarker to guide such targeted treatment strategies.[2][3][7]

Other names

NRASN-RasGTPase NRasNeuroblastoma RAS viral oncogeneNRAS proto-oncogene GTPase

Indirect inhibition of **mutated NRAS signaling** via inhibition of downstream MEK1/2 in the RAF–MEK–ERK pathway (MEK inhibitors such as binimetinib, trametinib, cobimetinib); Indirect reduction of NRAS‑driven proliferation and survival signaling through blockade of MAPK signaling; Experimental strategies aimed at inhibiting NRAS–RAF interaction or downstream effectors (class concepts)