Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2017; 23(13): 2276-2285
Published online Apr 7, 2017. doi: 10.3748/wjg.v23.i13.2276
Advanced pancreatic ductal adenocarcinoma - Complexities of treatment and emerging therapeutic options
Chandra Diwakarla, Katherine Hannan, Nadine Hein, Desmond Yip
Chandra Diwakarla, Desmond Yip, Department of Medical Oncology, The Canberra Hospital, Woden ACT 2605, Australia
Chandra Diwakarla, Katherine Hannan, Nadine Hein, The John Curtin School of Medical Research, Australian National University, Acton ACT 2601, Australia
Desmond Yip, ANU Medical School, Australian National University, Canberra ACT 0200, Australia
Author contributions: Diwakarla C wrote the manuscript with significant input from Hein N and Hannan K regarding the scientific data for nucleolar stress and prior experiments; Hein N, Hannan K and Yip D provided substantial assistance in the final editing and layout of the information.
Conflict-of-interest statement: The authors have no conflict of interest associated with this review.
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:
Correspondence to: Chandra Diwakarla, BSc(Hons), MBBS, Oncology Fellow, Department of Medical Oncology, The Canberra Hospital, Yamba Drive, Woden ACT 2605, Australia.
Telephone: +61-2-62442220 Fax: +61-2-62444266
Received: November 23, 2016
Peer-review started: November 25, 2016
First decision: December 19, 2016
Revised: January 18, 2017
Accepted: March 15, 2017
Article in press: March 15, 2017
Published online: April 7, 2017

Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental improvements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel therapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results. This review will focus on the current therapeutic options for pancreatic ductal adenocarcinoma and the complexities associated with developing novel treatments, with a particular emphasis on the role of the nucleolus as a treatment strategy.

Keywords: Ribosome biogenesis, Nucleolar stress, RNA polymerase I, Pancreatic ductal adenocarcinoma, Chemotherapy

Core tip: This manuscript is a review of the complexities involved in the treatment of advanced pancreatic ductal adenocarcinoma. It details the current approaches to therapy and the disease factors which have impacted on progress thus far. This review identifies the possible role of nucleolar stress as a treatment modality based on recent data from studies of haematological malignancies and some other solid organ cancers and explains the basic science involved in this process.