Abstract
Pancreatic adenocarcinoma remains one of the most aggressive cancers with an ongoing dismal survival rate despite some recent advances in treatment options. This is largely due to the typically late presentation and limited effective therapeutic options in advanced disease. There are numerous circulating biomarkers that have potential clinical application as tumour markers, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free RNA (cfRNA), exosomes and circulating tumour proteins. This review will focus on the development of ctDNA as a non-invasive liquid biopsy, with its high sensitivity and specificity having potential clinical applications in pancreatic cancer. These include a role in screening, prognostication via the detection of minimal residual disease, early detection of recurrence, and for patients with advanced disease; tumour genotyping and monitoring treatment response. Prospective randomised adjuvant clinical trials are currently underway, exploring the impact of ctDNA-guided adjuvant therapy decisions. In this review, we provide perspectives on the current literature and considerations of future directions.
Highlights
Not a common cancer, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in developed countries and the seventh leading cause of cancer-related death worldwide [1,2]
In the last decade, some progress has been made in the treatment of advanced disease, with FOLFIRINOX chemotherapy extending median survival to 11 months [8], albeit with significant toxicity
With the goal of developing improved strategies to diagnose pancreatic cancer at earlier stages, much focus has been placed on blood biomarkers including “liquid biopsies” such as circulating tumour DNA (ctDNA)
Summary
Not a common cancer, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in developed countries and the seventh leading cause of cancer-related death worldwide [1,2]. CtDNA has been restricted in its clinical application until recently due to the incapacity to reliably detect and compute the extremely low frequency of DNA variants that may be present in a blood sample, in the context of screening of minimal residual disease. The single mutation or limited mutation panel strategy utilises detection of individual point mutations through polymerase chain reaction (PCR)-based assays, such as droplet digital PCR (ddPCR) and beads, emulsion, amplification and magnetics (BEAMing). These techniques offer greater sensitivity than non-targeted approaches, but necessitate prior knowledge of mutation information [17]. Further references to pancreatic cancer in this review will pertain to PDAC only
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