Zhang et al. reported re-activation of ERK after MEK inhibition in colorectal cancer cells which was overcome by cetuximab indicating that double MEK and EGFR blockade are crucial in epithelial cancer.41 We and others have shown that the MAPK/ERK axis plays a significant role in the development of radioresistance in HNSCC.12,13,42 IR mediates pathway activation, which leads to reduced radiosensitivity. This evidence concerns the gene INSR and head and neck squamous cell carcinoma.