Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

International Journal of Molecular Sciences

Antonio Gnoni³  Antonella Licchetta³  Aldo Scarpa⁷  Amalia Azzariti⁸  Anna Elisabetta Brunetti²  Gianni Simone⁴  Patrizia Nardulli⁶  Daniele Santini¹  Michele Aieta⁵  Sabina Delcuratolo² 

[1] Medical Oncology Department, University Campus Bio-Medico, Rome 00199, Italy; E-Mail:;Scientific Direction, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy; E-Mail:;Medical Oncology Unit, Hospital Vito Fazzi, Lecce 73100, Italy; E-Mails:;Histopathology Unit, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy; E-Mail:;Medical Oncology Unit - CROB-IRCCS, 85028, Rionero in Vulture, Potenza 85100, Italy; E-Mail:;Hospital Pharmacy Unit - National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy; E-Mail:;Department of Pathology and Diagnostics, University of Verona, Verona 37121, Italy; E-Mail:;Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy; E-Mail:

关键词: carcinogenesis;    micro-RNAs;    oncogenes;    pancreatic adenocarcinoma;    precursor lesions;   

DOI  :  10.3390/ijms141019731

来源: mdpi

【 摘 要 】

Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland