title: Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ; Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Garajová
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Tessa Y
authors.initials: TY
authors.lastname: Le Large
authors.affiliation: HPB Surgical Unit, Department of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, White City, London W12 0NN, UK.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Phase I-Early Clinical Trials Unit, Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.
authors.forename: Christian
authors.identifier: 0000-0002-5109-0267
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Voortman
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ; Start-Up Unit, University of Pisa, Lungarno Pacinotti 43, 56126 Pisa, Italy.
authors.forename: Elisa
authors.identifier: 0000-0002-7565-7504
authors.initials: E
authors.lastname: Giovannetti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D009363:Neoplasm Proteins