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Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells. Next, we will explore the characteristics and merits of the different mouse models of PDAC. The inflammatory milieu and the immunosuppressive microenvironment mediate tumour initiation and treatment failure. Hence, we will also review the inflammatory and immune escaping mechanisms and the new immunotherapies tested in PDAC. A better understanding of the different mechanisms of tumour formation and progression will help us to identify the best targets for testing in future clinical studies of PDAC.

Original publication

DOI

10.1016/j.bbcan.2014.12.001

Type

Journal article

Journal

Biochim Biophys Acta

Publication Date

01/2015

Volume

1855

Pages

61 - 82

Keywords

Biology, Chemotherapy, Genetics, Oncoimmunology, Pancreatic cancer, Radiobiology, Animals, Cancer Vaccines, Carcinoma, Pancreatic Ductal, Cell Transformation, Neoplastic, Disease Models, Animal, Drug Resistance, Neoplasm, Humans, Immunotherapy, Inflammation, Mice, Neoplastic Cells, Circulating, Pancreatic Neoplasms, Radiation Tolerance