Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

Abstract

Reliable biomarkers are required to evaluate and manage pancreatic ductal adenocarcinoma. Circulating tumor cells and circulating tumor DNA are shed into blood and can be relatively easily obtained from minimally invasive liquid biopsies for serial assays and characterization, thereby providing a unique potential for early diagnosis, forecasting disease prognosis, and monitoring of therapeutic response. In this review, we provide an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and describe recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma.

Keywords: circulating tumor DNA; circulating tumor cells; liquid biopsy; pancreatic cancer; pancreatic ductal adenocarcinoma; tumor-derived circulating cell-free DNA.

Figure 1

Examples of technology platforms for detecting circulating tumor DNA and limit of detection ranges. These depend on number of mutations measured and quantity of DNA present in a blood sample. Optimized NGS techniques provide sequencing error correction. Other ctDNA assays being applied to pancreatic cancer include personalized panels and commercially available tests. PCR: polymerase chain reaction; NGS: next‐generation sequencing; ARMS: amplification‐refractory mutation system; COLD‐PCR: coamplification at lower denaturation temperature PCR; Cast‐PCR: competitive allele‐specific TaqMan PCR; LNA‐dPNA PCR: locked nucleic acid‐dual peptide nucleic acid PCR clamp; ddPCR: droplet digital PCR; BEAMing: beads, emulsion, amplification, and magnetics digital PCR; TAm‐Seq: tagged‐amplicon deep sequencing; CAPP‐Seq/iDES: cancer personalized profiling by deep sequencing with integrated digital error suppression; BPER: base‐position error rate.