KRAS抗体—艾普蒂

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     Gel: 12%SDS-PAGE, Lysate: 40 μg, Lane 1-2: RAMOS cell, Mouse brain tissue lysates, Primary antibody: P06880(KRAS Antibody) at dilution 1/500, Secondary antibody: Goat anti rabbit IgG at 1/5000 dilution, Exposure time: 40 seconds    

  
  

The KRAS protein, encoded by the KRAS gene, is a critical signaling molecule in the Ras/MAPK pathway, regulating cell proliferation, differentiation, and survival. Mutations in KRAS are among the most common oncogenic drivers, occurring in ~25% of human cancers, including pancreatic, colorectal, and lung adenocarcinomas. These mutations (e.g., G12D, G12V, G13D) lock KRAS in a constitutively active GTP-bound state, promoting uncontrolled cell growth. For decades, KRAS was deemed "undruggable" due to its smooth surface, high GTP affinity, and lack of deep binding pockets for small molecules.

Antibody-based targeting of KRAS faced similar challenges. Traditional monoclonal antibodies struggled to block KRAS activity directly, as intracellular localization limited accessibility. However, advances in antibody engineering, including nanobodies, bispecific formats, and covalent binders, have enabled novel approaches. For example, allele-specific antibodies targeting mutant KRAS (e.g., anti-KRAS G12D) exploit unique neoantigenic epitopes, offering precision in distinguishing mutated from wild-type proteins. Others inhibit KRAS-effector interactions or target KRAS membrane localization by disrupting its interaction with PDEδ.

KRAS antibodies also serve as diagnostic tools, detecting mutation status in tumors via IHC or liquid biopsies. While no KRAS-targeting antibody has yet gained clinical approval, preclinical models show promise, particularly in combination with immune checkpoint inhibitors or RAS pathway inhibitors. Ongoing research focuses on improving delivery, specificity, and overcoming resistance mechanisms.