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Challenges of drug resistance in the management of pancreatic cancer

Sheikh, Rizwan and Walsh, Naomi and Clynes, Martin and O'Connor, Robert and McDermott, Ray (2010) Challenges of drug resistance in the management of pancreatic cancer. Expert Review of Anticancer Therapy, 10 (10). pp. 1647-1661. ISSN 1473-7140

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Abstract

The current treatment of choice for metastatic pancreatic cancer involves single agent gemcitabine or combination of gemcitabine with capecitabine and erlotinib (tyrosine kinase inhibitor). Only 25-30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activations of DNA repair pathways, resistance to apoptosis, and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, over expression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target, and/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

Item Type:Article (Published)
Refereed:Yes
Additional Information:Expert Reviews require 12 embargo unless explicit permission is obtained. Their permissions service has been contacted but until the respond the item will remain embargoed until 31st October 2011.
Uncontrolled Keywords:Pancreatic cancer; Drug resistance; anticancer therapy; Capecitabine; Gemcitabine; Erlotinib; Tyrosine Kinase Inhibitor
Subjects:Medical Sciences > Cancer
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Nursing and Human Sciences
Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Publisher:Expert Reviews
Official URL:http://www.expert-reviews.com/doi/abs/10.1586/era.10.148
Copyright Information:) Manuscripts that have been submitted for publication and entry into peer review Once a manuscript has been submitted for publication and entered into peer review, authors may share print or electronic copies of an article with colleagues. In doing so, they should state that the article has been submitted for publication to [the specified journal]. The author(s) may also post an electronic version of an article on a personal website, the website of an employer or institution, or to free public servers.
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
ID Code:16057
Deposited On:11 May 2011 16:40 by Naomi Walsh. Last Modified 06 Dec 2011 11:38

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