For pancreatic cancer, Grp78 haploinsufficiency suppressed AKT, S6, extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 activation, and reduced epidermal growth factor receptor (EGFR) protein level critical for acinar-to-ductal metaplasia initiation, a key step in pancreatic tumorigenesis (49). This evidence concerns the gene HSPA5 and familial pancreatic carcinoma.