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

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...

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Autores principales: Moutinho-Ribeiro, Pedro, Macedo, Guilherme, Melo, Sónia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331408/
https://www.ncbi.nlm.nih.gov/pubmed/30671023
http://dx.doi.org/10.3389/fendo.2018.00779
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author Moutinho-Ribeiro, Pedro
Macedo, Guilherme
Melo, Sónia A.
author_facet Moutinho-Ribeiro, Pedro
Macedo, Guilherme
Melo, Sónia A.
author_sort Moutinho-Ribeiro, Pedro
collection PubMed
description 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.
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spelling pubmed-63314082019-01-22 Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble? Moutinho-Ribeiro, Pedro Macedo, Guilherme Melo, Sónia A. Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2019-01-08 /pmc/articles/PMC6331408/ /pubmed/30671023 http://dx.doi.org/10.3389/fendo.2018.00779 Text en Copyright © 2019 Moutinho-Ribeiro, Macedo and Melo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Moutinho-Ribeiro, Pedro
Macedo, Guilherme
Melo, Sónia A.
Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title_full Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title_fullStr Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title_full_unstemmed Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title_short Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble?
title_sort pancreatic cancer diagnosis and management: has the time come to prick the bubble?
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331408/
https://www.ncbi.nlm.nih.gov/pubmed/30671023
http://dx.doi.org/10.3389/fendo.2018.00779
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