Considering that both anti-mTOR, anti-PI3K, and anti-EGFR therapies are already in routine clinical use or in late clinical development for a number of other cancer histologies, these observations suggest that PI3K and mTOR inhibitors may be considered for molecular-targeted therapies within clinical studies for patients with HDGC in the near future. This evidence concerns the gene EGFR and CDH1-related diffuse gastric and lobular breast cancer syndrome.