Liquid biopsies in pancreatic cancer

ABSTRACT

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a disease of high lethality. Invasive tissue biopsies of primary or metastatic lesions remain the gold standard for diagnosis, but repeated sampling is infeasible. Noninvasive liquid biopsies offer new opportunities for early diagnosis for high-risk cohorts, and for the longitudinal analysis of tumor evolution and progression in patients on therapy. Liquid biopsies can capture tumor-associated components, such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), each of which provides genomic and molecular information about the underlying PDAC that can potentially inform clinical decisions.

Areas covered: Here, we reviewed current knowledge and recent technological advances regarding liquid biopsy in PDAC and mention the pitfalls and benefits in each methodology. We also discuss clinical correlative studies for diagnosis and prognosis in PDAC.

Expert opinion:In pancreatic cancer where tissue samples are limited and repeated tissue biopsies are mostly invasive and infeasible, liquid biopsies opened a new window for tumor diagnosis, molecular stratification, and treatment monitoring. While none of the isolation and analysis methods have gained widespread clinical acceptance, it is imperative that the advantages and limitations of each platform for isolation and analysis of tumor associated components are taken into consideration.

KEYWORDS:

• Cell-free DNA
• circulating tumor cells
• extracellular vesicles
• liquid biopsies
• pancreatic cancer

Article highlights

• Standard clinical methods for diagnosing pancreatic cancer include assessment of tissue biopsies and aspiration cytology specimens, and noninvasive screening methods (e.g. computed tomography [CT], magnetic resonance imaging, endoscopic ultrasonography [EUS]). However, these are typically used in symptomatic patients and not in the context of early detection.

• Liquid biopsies involve isolation of tumor-released components from bodily fluids, including circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), which can be beneficial for diagnosis and prognosis of PDAC.

• Methods for isolating EVs and CTCs include size-, density-, affinity-, or external field–based separation principles.

• Droplet digital polymerase chain reaction (ddPCR) and next generation sequencing (NGS) for DNA using targeted panels are the two most commonly used methods for assessment of the mutational events in liquid biopsies.

• Many challenges exist for reliable isolation of tumor associated components such as circulating tumor cells and EVs from blood of pancreatic cancer patients.

Declaration of interest

Anirban Maitra has received royalties from Cosmos Wisdom Biotechnology Company LTD for being a co-inventor on a license related to pancreatic cancer early detection, and this financial relationship is managed by the MD Anderson Conflict of Interest Committee. Editorial assistance was provided by Joseph Munch, Department of Scientific Publications, UT MD Anderson Cancer Center. There are no other conflicts of interests to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the Cancer Prevention and Research Institute of Texas-research training program (RP140106 and RP170067) and the National Cancer Institute (T32CA217789-03, U54CA096297, U01CA196403, U01CA200468, R01CA218004, and R01CA218230).