Advanced pancreatic ductal adenocarcinoma - Complexities of treatment and emerging therapeutic options

Abstract

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.