Investigational biomarkers for pancreatic adenocarcinoma: where do we stand?

Although the outcomes for pancreatic ductal adenocarcinoma (PDAC) remain disappointing, there has been considerable improvement in the 5-year survival rate of patients with resectable disease. As such, an R0 surgical resection (microscopic tumor clearance) offers patients with PDAC the greatest survival benefit. Carbohydrate antigen 19-9, the only US Food and Drug Administration-approved biomarker for PDAC, is a poor screening tool and is most informative after PDAC resection. Consequently, there has been a tremendous initiative to discover novel biomarkers that may aid in detecting the disease earlier, improving prognosis, and predicting response to available chemotherapy. The number of implicated biomarkers in PDAC is indeed staggering, with >2500 proposed candidates presented in the recent literature. A vast majority of these biomarkers, however, remain in the investigational phase. This review categorizes the most promising biomarkers--those closest to potential clinical application--into diagnostic and prognostic/predictive groups. The greatest challenge likely lies in the search for an effective diagnostic biomarker that can accurately discriminate between malignant and benign disease, and thereby facilitate earlier identification of those patients with PDAC who may benefit most from surgical resection.