One could further speculate that the synergy between EGFR inhibition and metformin may occur in other tumor types enriched for concurrent EGFR and PI3K pathway activation, including squamous cell cancers, colorectal cancer, glioblastoma with EGFR vIII amplification, and lung cancer with EGFR exon 18 through 21 mutations. This evidence concerns the gene PIK3CA and squamous cell carcinoma.