Hence, loss of suppression of EGFR signaling by lack of E-cadherin/catenin–EGFR interaction in HDGC families with CDH1 germline mutations might explain the increased sensitivity to EGFR and PI3K kinase inhibition in CDH1-deficient HDGC (Fig. 1). This evidence concerns the gene EGFR and CDH1-related diffuse gastric and lobular breast cancer syndrome.