The KRAS, HRAS, and NRAS proteins belong to the RAS family of small GTPases, which play pivotal roles in regulating cell signaling pathways involved in proliferation, differentiation, and survival. These proteins cycle between inactive GDP-bound and active GTP-bound states, acting as molecular switches. Mutations in RAS genes (particularly KRAS, which is most frequently altered) are common in human cancers, leading to constitutive activation of downstream pathways like MAPK/ERK, driving uncontrolled cell growth and tumor progression.
Antibodies targeting KRAS, HRAS, and NRAS are critical tools for studying their expression, localization, and post-translational modifications in both normal and diseased states. Due to the high sequence homology (∼85%) among these isoforms, developing isoform-specific antibodies has been challenging. However, advances in epitope mapping and recombinant antibody technologies have improved specificity. These antibodies are widely used in techniques such as Western blotting, immunohistochemistry (IHC), and immunofluorescence to assess RAS overexpression or mutation status in tumor samples.
In clinical diagnostics, RAS mutation-specific antibodies (e.g., anti-KRAS G12D/G12V) help stratify patients for targeted therapies, such as EGFR inhibitors in colorectal cancer, where KRAS mutations confer treatment resistance. Similarly, NRAS mutations in melanoma and HRAS alterations in bladder/thyroid cancers guide therapeutic decisions. Despite challenges in cross-reactivity, RAS antibodies remain indispensable for both basic research and precision oncology applications.