Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2015; 21(20): 6127-6145
Published online May 28, 2015. doi: 10.3748/wjg.v21.i20.6127
New targeted therapies in pancreatic cancer
Andrada Seicean, Livia Petrusel, Radu Seicean
Andrada Seicean, Livia Petrusel, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 4000192, Romania
Radu Seicean, First Surgery Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 4000192, Romania
Author contributions: Seicean A and Seicean R reviewed the literature; Seicean A, Petrusel L and Seicean R wrote the paper.
Conflict-of-interest: The authors have no conflicts of interests to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrada Seicean, MD, PhD, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, 19-21 Croitorilor Street, Cluj-Napoca 400162, Romania. andradaseicean@gmail.com
Telephone: +40-744-332107 Fax: +40-264-431758
Received: December 12, 2014
Peer-review started: December 12, 2014
First decision: February 2, 2015
Revised: February 26, 2015
Accepted: April 16, 2015
Article in press: April 17, 2015
Published online: May 28, 2015
Processing time: 169 Days and 8.2 Hours
Abstract

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Keywords: Immunotherapy; Pancreas neoplasm; Vaccines

Core tip: Adjuvant therapy in pancreatic cancer has limited efficiency, and low survival rates are related to resistance to gemcitabine. New targeted therapies, such as passive immunotherapy, may have a role in combination with radiochemotherapy by targeting various protein kinases, as well as specific immunotherapies, such as vaccines, adoptive cell therapy and immunotherapy targeting tumor stem cells. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.