Biomarkers for early diagnosis of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a 5-year survival rate of approximately 5%. The lack of established strategies for early detection contributes to this poor prognosis. Although several novel candidate biomarkers have been proposed for earlier diagnosis, none have been adopted into routine clinical use. In this review, the authors examine the challenges associated with finding new pancreatic cancer diagnostic biomarkers and explore why translation of biomarker research for patient benefit has thus far failed. The authors also review recent progress and highlight advances in the understanding of the biology of pancreatic cancer that may lead to improvements in biomarker detection and implementation.

Keywords:

• biomarker
• diagnosis
• jaundice
• pancreatic cancer

Financial & competing interests disclosure

C Jenkinson is supported by Northwest Cancer Research Fund, UK, grant CR976. Additional support is from the National Institute for Health Research Liverpool Pancreas Biomedical Research Unit and the European Cooperation in Science and Technology (COST Action #BM1204: EU_Pancreas). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pancreatic ductal adenocarcinoma has a poor 5-year survival rate, which has remained unchanged for over four decades.

• The disease is almost always detected when at an advanced stage, hence biomarkers to facilitate earlier disease detection, when there are greater opportunities for effective treatment, are urgently sought.

• The incidence of pancreatic cancer is low. Biomarkers for use in screening therefore need to be highly specific so that the number of false positives does not exceed the number of true positives.

• Translation of biomarkers to clinical use to date has failed for a variety of reasons, including failure to include appropriate controls such as chronic pancreatitis and failure to account for confounding factors such as biliary obstruction and diabetes.

• Understanding the phenotypic nature of circulating pancreatic cancer cells could accelerate the development of methods for circulating pancreatic tumor cell detection.

• The use of prediagnostic cohorts has a potentially valuable role in both the discovery of new diagnostic biomarkers and in the validation of existing candidates.

• Improvements in imaging, enabling the detection of very small tumors or precursor lesions such as pancreatic intraepithelial neoplasia, could radically improve diagnosis and may be key to the implementation of early circulating biomarkers.

• Advances in early detection, if supported by concurrent improvements in treatment, could bring enormous patient benefit.

• For a cost–effective diagnostic biomarker of pancreatic ductal adenocarcinoma, exquisitely high sensitivity and specificity are required.

Notes