ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?

© The Author(s) 2018. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in canc...

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Main Authors: Adamska, A., Falasca, Marco
Format: Journal Article
Published: Baishideng BioMed Scientific Co., Ltd 2018
Online Access:http://hdl.handle.net/20.500.11937/72542
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author Adamska, A.
Falasca, Marco
author_facet Adamska, A.
Falasca, Marco
author_sort Adamska, A.
building Curtin Institutional Repository
collection Online Access
description © The Author(s) 2018. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATPbinding cassette (ABC) transporters in this resistance, the therapeutic potential of their pharmacological inhibition has not been successfully exploited yet. In spite of the discovery of potent pharmacological modulators of ABC transporters, the results obtained in clinical trials have been so far disappointing, with high toxicity levels impairing their successful administration to the patients. Critically, although ABC transporters have been mostly studied for their involvement in development of multidrug resistance (MDR), in recent years the contribution of ABC transporters to cancer initiation and progression has emerged as an important area of research, the understanding of which could significantly influence the development of more specific and efficient therapies. In this review, we explore the role of ABC transporters in the development and progression of malignancies, with focus on PDAC. Their established involvement in development of MDR will be also presented. Moreover, an emerging role for ABC transporters as prognostic tools for patients' survival will be discussed, demonstrating the therapeutic potential of ABC transporters in cancer therapy.
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spelling curtin-20.500.11937-725422019-03-21T01:39:39Z ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward? Adamska, A. Falasca, Marco © The Author(s) 2018. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATPbinding cassette (ABC) transporters in this resistance, the therapeutic potential of their pharmacological inhibition has not been successfully exploited yet. In spite of the discovery of potent pharmacological modulators of ABC transporters, the results obtained in clinical trials have been so far disappointing, with high toxicity levels impairing their successful administration to the patients. Critically, although ABC transporters have been mostly studied for their involvement in development of multidrug resistance (MDR), in recent years the contribution of ABC transporters to cancer initiation and progression has emerged as an important area of research, the understanding of which could significantly influence the development of more specific and efficient therapies. In this review, we explore the role of ABC transporters in the development and progression of malignancies, with focus on PDAC. Their established involvement in development of MDR will be also presented. Moreover, an emerging role for ABC transporters as prognostic tools for patients' survival will be discussed, demonstrating the therapeutic potential of ABC transporters in cancer therapy. 2018 Journal Article http://hdl.handle.net/20.500.11937/72542 10.3748/wjg.v24.i29.3222 https://creativecommons.org/licenses/by-nc/4.0/ Baishideng BioMed Scientific Co., Ltd fulltext
spellingShingle Adamska, A.
Falasca, Marco
ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title_full ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title_fullStr ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title_full_unstemmed ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title_short ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?
title_sort atp-binding cassette transporters in progression and clinical outcome of pancreatic cancer: what is the way forward?
url http://hdl.handle.net/20.500.11937/72542