Recent Discoveries of Diagnostic, Prognostic and Predictive Biomarkers for Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a dismal prognosis that is frequently diagnosed at an advanced stage. Although less common than other malignant diseases, it currently ranks as the fourth most common cause of cancer-related death in the European Union with a five-year survival rate of below 9%. Surgical resection, followed by adjuvant chemotherapy, remains the only potentially curative treatment but only a minority of patients is diagnosed with locally resectable, non-metastatic disease. Patients with advanced disease are treated with chemotherapy but high rates of treatment resistance and unfavorable side-effect profiles of some of the used regimens remain major challenges. Biomarkers reflect pathophysiological or physiological processes linked to a disease and can be used as diagnostic, prognostic and predictive tools. Thus, accurate biomarkers can allow for better patient stratification and guide therapy choices. Currently, the only broadly used biomarker for PDAC, CA 19-9, has multiple limitations and the need for novel biomarkers is urgent. In this review, we highlight the current situation, recent discoveries and developments in the field of biomarkers of PDAC and their potential clinical applications.

Keywords: DNA biomarkers; immune biomarkers; metabolome biomarkers; microbiome biomarkers; pancreatic cancer; pancreatic ductal adenocarcinoma; protein biomarkers.

Figure 1

Immune infiltrates of pancreatic ductal adenocarcinoma form an immune suppressive environment. Anti-tumor immunity is suppressed through T-cell apoptosis, inhibition of cytotoxic T-cell recruitment and reduced secretion of pro-inflammatory cytokines, such as IL-4 and IL-5. PD-L1: Programmed death-ligand 1, Treg: regulatory T-cell, myCAFs: myofibroblastic cancer-associated fibroblast (CAF), iCAFs: inflammatory CAFs, apCAFs: antigen-presenting CAFs. Created with BioRender.com.