Format

Send to

Choose Destination
Cancers (Basel). 2017 Nov 16;9(11). pii: E157. doi: 10.3390/cancers9110157.

Pancreatic Cancer Chemoresistance to Gemcitabine.

Author information

1
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, PO Box 1057 Blindern, 0316 Oslo, Norway. manoj.amrutkar@medisin.uio.no.
2
Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, PO Box 1171 Blindern, 0318 Oslo, Norway. manoj.amrutkar@medisin.uio.no.
3
Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, PO Box 1171 Blindern, 0318 Oslo, Norway. i.p.gladhaug@medisin.uio.no.
4
Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway. i.p.gladhaug@medisin.uio.no.

Abstract

Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation. To circumvent gemcitabine resistance in PDAC, several novel therapeutic approaches, including chemical modifications of the gemcitabine molecule generating numerous new prodrugs, as well as new entrapment designs of gemcitabine in colloidal systems such as nanoparticles and liposomes, are currently being investigated. Many of these approaches are reported to be more efficient than the parent gemcitabine molecule when tested in cellular systems and in vivo in murine tumor model systems; however, although promising, their translation to clinical use is still in a very early phase. This review discusses gemcitabine metabolism, activation and chemoresistance entities in the gemcitabine cytotoxicity pathway and provides an overview of approaches to override chemoresistance in pancreatic cancer.

KEYWORDS:

chemoresistance; gemcitabine; pancreatic ductal adenocarcinoma; tumor stroma

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center