Why Cetuximab Stops Working in Head and Neck Cancer: ERK Reactivation at the Center
- Cetuximab is the only approved molecularly targeted agent against a tumor receptor in head and neck squamous cell carcinoma, yet response rates are low and resistance is common.
- The review groups resistance into EGFR alterations, compensatory parallel pathways and reactivation of PI3K/Akt and Ras/ERK signaling.
- It treats ERK as the integrator of genetic, epigenetic and adaptive resistance.
💡 Points Based on the abstract
Framing ERK as the convergence point is attractive because it suggests a common combination partner, but ERK reactivation is a readout of many upstream events and clinical ERK-pathway combinations have been hard to tolerate. The missing piece is patient-level data on which mechanism operates in which tumor. Without a biomarker that predicts the escape route, the combination trials will stay unselected.
📄 Paper · Biochemical Pharmacology ↗ Mechanisms of cetuximab resistance in head and neck squamous cell Carcinoma: Focus on the EGFR–ERK pathway