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Review
. 2019 Jan 8;9:779.
doi: 10.3389/fendo.2018.00779. eCollection 2018.

Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?

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Free PMC article
Review

Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?

Pedro Moutinho-Ribeiro et al. Front Endocrinol (Lausanne). .
Free PMC article

Abstract

Pancreatic cancer (PC) is associated with poor prognosis and very dismal survival rates. The most effective possibility of cure is tumor resection, which is only possible in about 15% of patients diagnosed at early stages of disease progression. Recent whole-genome sequencing studies pointed genetic alterations in 12 core signaling pathways in PC. These observations hint at the possibility that the initial mutation in PC might appear nearly 20 years before any symptoms occur, suggesting that a large window of opportunity may exist for early detection. Biomarkers with the potential to identify pre-neoplastic disease or very early stages of cancer are of great promise to improve patient survival. The concept of liquid biopsy refers to a minimally invasive sampling and analysis of liquid biomarkers that can be isolated from body fluids, primarily blood, urine and saliva. A myriad of circulating molecules may be useful as tumor markers, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), circulating tumor proteins, and extracellular vesicles, more specifically exosomes. In this review, we discuss with more detail the potential role of exosomes in several aspects related to PC, from initiation to tumor progression and its applicability in early detection and treatment. Exosomes are small circulating extracellular vesicles of 50-150 nm in diameter released from the plasma membrane by almost all cells and exhibit some advantages over other biomarkers. Exosomes are central players of intercellular communication and they have been implicated in a series of biological process, including tumorigenesis, migration and metastasis. Several exosomal microRNAs and proteins have been observed to distinguish PC from benign pancreatic diseases and healthy controls. Besides their possible role in diagnosis, understanding exosomes functions in cancer has clarified the importance of microenvironment in PC progression as well as its influence in proliferation, metastasis and resistance to chemotherapy. Increasing knowledge on cancer exosomes provides valuable insights on new therapeutic targets and can potentially open new strategies to treat this disease. Continuous research is needed to ascertain the reliability of using exosomes and their content as potential biomarkers, so that, hopefully, in the near future, they will provide the opportunity for early diagnosis, treatment intervention and increase survival of PC patients.

Keywords: biomarkers; early diagnosis; exosomes; liquid biopsy; pancreatic cancer.

Figures

Figure 1
Figure 1
Timeline of development of pancreatic cancer diagnostic and staging modalities. Pancreatic cancer (PC) diagnosis and staging depends, substantially, on imaging modalities. Abdominal Ultrasonography (US) was the first to appear, but lacks sensitivity to detect small treatable lesions. Multidetector computed tomography (MDCT) is nowadays frequently used to detect and stage pancreatic masses, with good accuracy specially for 2 cm and larger lesions. Magnetic resonance imaging (MRI) and its variant magnetic resonance cholangiopancreatography (MRCP) improved the sensitivity for characterization small cystic lesions. More recently, endoscopic ultrasonography (EUS) with the possibility to perform fine needle aspiration (FNA) constitutes a prime modality for precise diagnosis and local staging of small (< 2 cm) solid and cystic pancreatic lesions. The innovative concept of liquid biopsy refers to a simple and painless collection of a body fluid sample (usually blood), in order to study proved and anticipated biomarkers with the potential to detect PC in its early non detectable stages and even the premalignant precursors.
Figure 2
Figure 2
Current understanding of molecular biomarkers for pancreatic cancer. A myriad of circulating molecules may be used as tumor markers, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), circulating tumor proteins, and extracellular vesicles, more specifically exosomes. The characterization of these tumor biomarkers favors improvement of the knowledge of tumor heterogeneity and, most importantly, contributes to early detection, monitoring of disease progression and response to treatment. Moreover, some of these molecules, in the near future, can play a role as therapeutic targets, hopefully allowing the control of the disease during its early curable stages.

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