Mechanisms of development and progression of pancreatic neoplasms

• Published in: Pathology international Vol. 72; no. 11; pp. 529 - 540
• Main Author: Furukawa, Toru
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.11.2022; John Wiley and Sons Inc
• Subjects: Adenocarcinoma; AURKA; Aurora Kinase A - genetics; Cancer; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Pancreatic Ductal - pathology; Cell proliferation; Dual Specificity Phosphatase 6 - genetics; DUSP6; Dysplasia; Effectors; Epithelium; GNAS; Health risks; Humans; IPMN; ITPN; Kinases; MAP kinase; MAPK; Medical prognosis; miRNA; Mutation; Neoplasia; Neoplasms; Pancreatic cancer; Pancreatic Intraductal Neoplasms - genetics; Pancreatic Intraductal Neoplasms - pathology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Papillae; Protein kinase; Review; RNF43; SON; Therapeutic targets; Tumors; RNF43; pancreatic cancer; SON; GNAS; miRNA; IPMN; ITPN; MAPK; DUSP6; AURKA
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/pin.13272

Pancreatic ductal adenocarcinoma (PDAC) develops via dysplastic changes in the epithelia graded as low‐ and high‐grade with accumulation of molecular alterations. Constitutive activation of mitogen‐activated protein kinase (MAPK) contributed by attenuation of DUSP6 plays a key role in sustaining PDAC. Active MAPK induces various molecules that function as effectors to sustain PDAC. AURKA and SON are downstream effectors that contribute substantially to the proliferation and survival of PDAC cells and are potentially useful as therapeutic targets. Active MAPK also promote microRNAs that modulate the proliferation of PDAC cells and are useful as diagnostic markers. Familial pancreatic cancer kindreds in Japan show various germline mutations supposed to increase a pancreatic cancer risk. Intraductal papillary mucinous neoplasms (IPMNs) consist of dilated ducts lined by papillary neoplastic epithelia of various shapes and varying grades of atypia. Various papillae of IPMNs are classified into four subtypes that are associated with clinicopathological features, including patient prognosis. GNAS is a specific driver gene for the development of IPMN through gain‐of‐function mutations. Tracing of molecular alterations has elucidated the mechanism of progression of IPMN from dysplasia to carcinoma, as well as one type of papillae. Intraductal tubulopapillary neoplasms belong to a distinct class of pancreatic neoplasms.