K-Ras

K-Ras (KRAS) is a small GTPase that functions as a molecular switch within the RAS/MAPK signaling network, cycling between inactive GDP-bound and active GTP-bound states to regulate cell proliferation, differentiation, and survival^[1][2]. Mechanistically, activated KRAS transduces signals from cell-surface receptors to downstream effectors, including the MAPK/ERK and PI3K/AKT pathways, thereby coordinating cellular growth and stress-response programs^[1][3]. Oncogenic mutations impair GTP hydrolysis and maintain persistent KRAS signaling, resulting in sustained activation of proliferative pathways that contribute to tumor initiation, progression, and therapeutic resistance across multiple cancer types, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer^[2][3][4]. In disease models, mutant KRAS also reshapes the tumor microenvironment through inflammatory and immune-regulatory signaling, further supporting tumor development and immune evasion^[3][2]. Compared with the related RAS isoforms HRAS and NRAS, KRAS is the most frequently altered RAS family member in human cancer and accounts for the majority of oncogenic RAS mutations, highlighting its distinct biological and clinical importance^[2][5]. For experimental applications, the development of mutation-selective inhibitors, especially KRAS^G12C^ inhibitors, has established a tractable platform for studying KRAS-dependent signaling and therapeutic resistance mechanisms, although resistance remains a major challenge for long-term clinical efficacy^[2][5].