Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Jun 9, 2015; 4(2): 180-192
Published online Jun 9, 2015. doi: 10.5497/wjp.v4.i2.180
Progress in pancreatic cancer therapeutics: The potential to exploit molecular targets
Kiruthikah Thillai, Debashis Sarker, Paul Ross
Kiruthikah Thillai, Debashis Sarker, Paul Ross, Department of Medical Oncology, Guy’s and St Thomas NHS Trust, SE19RT London, United Kingdom
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest: The authors declare no conflict of interest relevant to this article.
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: Dr. Paul Ross, Department of Medical Oncology, Guy’s and St Thomas NHS Trust, Great Maze Pond, SE19RT London, United Kingdom. paul.ross@gstt.nhs.uk
Telephone: +44-207-1887188 Fax: +44-207-1887534
Received: December 2, 2014
Peer-review started: December 2, 2014
First decision: February 7, 2015
Revised: March 9, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: June 9, 2015
Processing time: 199 Days and 7 Hours
Abstract

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though significant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. Recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be determined. For many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a significant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.

Keywords: Pancreatic cancer; Adenocarcinoma; Targeted therapy; Genomics; Stroma; KRAS; Chemotherapy

Core tip: Pancreatic ductal adenocarcinoma is a cancer with several significant genetic aberrations that have recently been identified by international research efforts. Despite these findings, standard therapy for advanced disease consists primarily of chemotherapy. In the last few years two new chemotherapy regimens, FOLFIRINOX and Gemcitabine/Nab-paclitaxel, have demonstrated survival benefits in large phase III trials resulting in a change to current practise. However, the advent of targeted treatments has not yet had a significant impact in this disease compared with other malignancies. Current research strategies include developing therapies directed towards the RAS-RAK-MEK pathway, PI3K-AKT-mTOR pathway, notch pathway and immunotherapies to name but a few, with several clinical trials underway. It is likely that the heterogeneous nature of pancreatic cancer necessitates a more personalised approach to management with targeted treatment guided by predictive biomarkers.