Clinical Interpretation:
The KRAS Q61H mutation is a recognized oncogenic driver, though less common than the G12X variants typically seen in non-small cell lung cancer (NSCLC). The high VAF (79.47%) suggests clonal dominance, indicating its likely role as the primary driver event.
Currently available KRAS inhibitors (e.g., sotorasib, adagrasib) specifically target the KRAS G12C mutation and are not effective against Q61H. However, this mutation does confer constitutive KRAS activation and downstream MAPK pathway signaling, which may have implications for experimental therapies under clinical investigation.
Therapeutic Implications:
• Targeted Therapy: No approved targeted agent for KRAS Q61H.
• Immunotherapy: May be considered depending on PD-L1 status, tumor mutational burden (TMB), and co-mutation landscape.
• Chemotherapy: Remains the standard backbone of systemic therapy.
• Clinical Trials: Enrollment in trials exploring pan-KRAS inhibitors or MAPK/ERK pathway modulators may be appropriate.
