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.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

“… 13 , 14 PDAC is a highly challenging neoplasm, still burdened with low survival rates, mainly due to late stage at diagnosis, early spread of micrometastatic disease, and poor response to cytotoxic agents, which represent the unique therapeutic option in most cases. 15 For carriers of gBRCA2 pathogenic variants, the lifetime risk of developing PDAC is estimated between 5% and 10%, while gBRCA1 pathogenic variants are associated with a two to four times increased risk of PDAC. 13 Overall, prevalence of these germline pathogenic variants varies from 5% to 9% in unselected PDAC populations to 15%-20% in familial PDAC.…”

Molecular advances in pancreatic cancer: A genomic, proteomic and metabolomic approach

“…Currently, the only biomarker for PDAC is carbohydrate antigen 19-9 (CA19-9), approved by the Food and Drug Administration for use in clinical practice[ 17 ]. Unfortunately, the median sensitivity and specificity of CA19-9 is 79% and 82% respectively, making it unsuitable for use as a diagnostic marker, with it being raised in other gastrointestinal pathology[ 18 ].…”

Mg2+ Transporters in Digestive Cancers

“…However, other cancers and benign diseases can cause CA 19-9 overexpression which can explain the poor specificity. Thus, there is an urgent need for specific biomarkers for PDAC [ 8 ]. To date, cigarette smoking and family history are the main risk factors but dietary style and obesity have been also considered [ 6 ].…”