K-Ras
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1. Ras
2. K-Ras
1. Ras
⑴ Involved in signal transduction as a GPCR activated by tyrosine kinases.
⑵ Plays a key role in activating MAPK.
⑶ Normal functions: cell proliferation, cell differentiation, and cell survival.
⑷ Ras is further classified into H-Ras, K-Ras, and N-Ras.
⑸ Hyperactivation of Ras can occur when GTPase-activating protein function is lost or when degradation-resistant proteins accumulate.
⑹ As a result, Ras can drive growth factor–independent cell proliferation, leading to oncogenic transformation.
⑺ Most growth factor–independent proliferation in cancer is caused by Ras activation.
2. K-Ras
⑴ K-Ras was discovered in 1983 as the first human oncogene.
⑵ It is one of the most common oncogenes, with K-Ras, H-Ras, and N-Ras mutations found in about 30% of all cancers.
⑶ Until 2021, no drugs targeting K-Ras–driven tumors had been approved.
① This has led major pharmaceutical companies to heavily invest in K-Ras–targeted drug development.
⑷ LUSC (Lung Squamous Cell Carcinoma):
① Accounts for 45% of all lung cancers.
② Smoke-driven.
③ Involves K-Ras.
④ Originates from basal epithelial cells.
⑸ Type 1. K-Ras G12C
① Two currently approved direct K-Ras G12C inhibitors: Sotorasib and Adagrasib.
② Lumakras (brand name) – Sotorasib (generic name)
○ Target: KRAS
○ Drug class: Signaling inhibitor
○ Indication: NSCLC (non-small cell lung cancer)
○ FDA approval: 2021
⑹ Type 2. K-Ras G12D
① One of the neoantigens formed in cancer cells when a specific mutation occurs in tumor DNA, creating a completely novel protein not present in normal cells.
⑺ Type 3. B-Raf Mutation
① Relationship between BRAF and K-Ras: part of the RAS–RAF–MEK–ERK signaling cascade (MAPK pathway).
② B-Raf mutations were discovered in 2002.
③ The first drug targeting B-Raf was approved in 2011.
Input: 2025.07.29 21:23