Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Although drug development over the past decade has gradually improved the prognosis of PDAC, the prognosis remains extremely poor. The predominant determinant of a poor prognosis is that patients are already at the advanced stage when they are diagnosed. Therefore, it is essential to detect early‐stage PDAC to ensure a good prognosis. However, in general, being asymptomatic at the early stage makes the detection of early‐stage PDAC very difficult. Recently, much attention has been focused on the utility of a liquid biopsy as a biomarker. Theoretically, early‐stage tumors can be detected even under asymptomatic conditions. A number of studies on liquid biopsies have been reported so far. Several biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCS), and exosomes, are used in liquid biopsies, with the potential to be applied to the clinical setting. Each biomarker is reported to have different utilities, such as the detection of early‐stage disease, the differential diagnosis of PDAC from other types of pancreatic tumors, the prediction of the prognosis or risk of recurrence, and monitoring the treatment response. In this review, we focus on ctDNA, CTCS, and exosomes as representative liquid biopsy biomarkers and describe the specific functions of each biomarker in the treatment of PDAC. Furthermore, we discuss the application of liquid biopsies, especially for the surgical management of PDAC.

Highlights

  • Pancreatic cancer is one of the deadliest cancers

  • The detection of mutations in the Kirsten rat sarcoma (KRAS) gene in Pancreatic ductal adenocarcinoma (PDAC) tissues obtained at an autopsy or surgically removed was reported in 1988.12 The KRAS mutation in blood from a pancreatic cancer patient was first detected using a liquid biopsy technique in 1994.13 The KRAS mutation occurs early during carcinogenesis[14] and is observed in more than 90% of PDAC cases

  • Pietrasz et al[20] reported that patients with circulating tumor DNA (ctDNA) detectable by at least one cancer-specific gene mutation, such as KRAS, tumor protein 53 (TP53), and SMAD family member4 (SMAD4), in the plasma collected after curative surgery had a significantly worse prognosis and shorter disease-free survival than those with undetectable ctDNA

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Summary

| INTRODUCTION

Pancreatic cancer is one of the deadliest cancers. Of the 18 million cancer cases diagnosed around the world in 2018, nearly half a million were estimated to be pancreatic cancer.[1]. Circulating tumor DNA came to be considered a suitable cancer biomarker due to the identification of KRAS mutations in ctDNA from the blood of PDAC patients.[13] The comprehensive genomic analysis for the cancers was expected to prove useful as a novel molecular diagnostic method. Pietrasz et al[20] reported that patients with ctDNA detectable by at least one cancer-specific gene mutation, such as KRAS, TP53, and SMAD4, in the plasma collected after curative surgery had a significantly worse prognosis and shorter disease-free survival than those with undetectable ctDNA. | 219 treatment response during treatment and longitudinal monitoring during surveillance.[27] if ctDNA is detected in preoperative blood samples from patients with pancreatic cancer, unnecessary laparotomy may be avoided, and it may help us choose chemotherapy before surgery. The molecules expressed on CTCs, including epithelial cell adhesion molecule (EpCAM) and E-cadherin, may change during EMT

| Methods of detecting CTCs
| SUMMARY AND FUTURE PERSPECTIVES
Findings
| CONCLUSIONS
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