title: Inhibition of progression of PanIN through antagonizing EGFR.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor with high lethality in humans. Pancreatic intraepithelial neoplasia (PanIN) is the predominant precancerous lesion for PDAC. Although PanIN is frequently detected in the normal and inflamed pancreas, only a few of PanIN eventually progress into PDAC. Thus, inhibition of PanIN-to-PDAC conversion is critical for preventing the occurrence of PDAC. Here, we evaluated the effect of inhibition of epidermal growth factor receptor (EGFR) signaling on the progression of low-grade PanIN into high-grade PDAC in an established mouse PDAC model (Ptf1a-Cre; K-rasG12D). We found that intraductal infusion of EGFR inhibitors at 12 weeks of age, which induced sustained inhibition of EGFR signaling in the pancreas, significantly decreased the incidence of high-grade PanIN in these mice at 24 weeks of age. Thus, our study suggests that inhibition of EGFR signaling may prevent development of PDAC.
authors.affiliation: Department of Hepatobiliary Surgery, Air Force General Hospital of PLA, 30th Fucheng Road, Beijing, 100142, China, hexiaojun38@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Xiao
authors.forename: Yalin
authors.initials: Y
authors.lastname: Kong
authors.forename: Wenbing
authors.initials: W
authors.lastname: Li
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D008297:Male; D008822:Mice, Transgenic; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage*; D020032:Tyrphostins / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; C509204:PD168393; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; C541485:EGFR protein, mouse; D066246:ErbB Receptors