Proteomic analysis of pancreatic ductal adenocarcinoma

ABSTRACT

Introduction

Pancreatic ductal adenocarcinoma (PDAC), which represents approximately 80% of all pancreatic cancers, is a highly aggressive malignant disease and one of the most lethal among all cancers. Overall, the 5-year survival rate among all pancreatic cancer patients is less than 9%; these rates have shown little change over the past 30 years. A more comprehensive understanding of the molecular mechanisms underlying this complex disease is crucial to the development of new diagnostic tools for early detection and disease monitoring, as well as to identify new and more effective therapeutics to improve patient outcomes.

Area covered

We summarize recent advances in proteomic strategies and mass spectrometry to identify new biomarkers for early detection and monitoring of disease progression, predict response to therapy, and to identify novel proteins that have the potential to be ‘druggable’ therapeutic targets. An overview of proteomic studies that have been conducted to further our mechanistic understanding of metastasis and chemotherapy resistance in PDAC disease progression will also be discussed.

Expert commentary

The results from these PDAC proteomic studies on a variety of PDAC sample types (e.g., blood, tissue, cell lines, exosomes, etc.) provide great promise of having a significant clinical impact and improving patient outcomes.

KEYWORDS:

• Biomarkers
• pancreatic ductal adenocarcinoma
• proteomics

Article highlights

• Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease and one of the most lethal among all cancers. The 5-year survival rate is only 2%. Despite improvements in surgical, chemotherapy and radiation techniques, pancreatic cancer, even when initially resectable, remains a highly lethal disease.

• Serum CA19-9, is the only FDA approved biomarker for PDAC in clinical use, but lacks specificity and sensitivity. It appears to be more useful as a marker of stage of disease or as an independent predictor of overall survival.

• Proteomic studies have identified many new potential PDAC-specific biomarkers, and the use of multi-biomarker panels are showing promise for the early detection of PDAC with increased specificity and selectivity compared to using CA 19-9 alone.

• Proteomic studies on patient clinical material (including precursor lesions of PDAC, PDAC primary tumor tissue and metastatic lesions) have identified proteins that have the potential to predict response to treatments, to stratify patients for specific therapies or as novel drug targets for new therapeutic approaches.

• An increased number of studies on identifying and characterising post-translational modifications in PDAC disease have been carried out over the past few years and have revealed potential roles for glycosylation, phosphorylation and S-nitrosylation in PDAC disease progression.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Science Foundation Ireland (SFI) under the US-Ireland R&D Partnership Program (grant no. SFI/14/US/B2997), and The Collaborative Research Program on Radiation Biology and Proteomics of Pancreatic Cancer funded from St. Luke’s Institute for Cancer Research, Dublin, Ireland.