Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Abstract

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas's poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.

Keywords: ctDNA; digital-droplet PCR (ddPCR); pancreatic cancer; pancreatic ductal adenocarcinoma (PDAC).

Figure 1

Circulating-tumor DNA (ctDNA) as a promising non-invasive blood-based biomarker in cancer management. Quantitative detection of ctDNA is based on the identification of various tumor-specific genetic or epigenetic aberrations in plasma cell-free DNA (cfDNA) samples.

Figure 2

Overview of the mutation screening process. Summary of both advantages and disadvantages of the technology disclosed and other putative applications.