Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine

Conway, J. R.W., Herrmann, D., Evans, T.R. J. , Morton, J. P. and Timpson, P. (2019) Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine. Gut, 68(4), pp. 742-758. (doi: 10.1136/gutjnl-2018-316822) (PMID:30396902) (PMCID:PMC6580874)

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Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly solid tumours. This is due to a generally late-stage diagnosis of a primarily treatment-refractory disease. Several large-scale sequencing and mass spectrometry approaches have identified key drivers of this disease and in doing so highlighted the vast heterogeneity of lower frequency mutations that make clinical trials of targeted agents in unselected patients increasingly futile. There is a clear need for improved biomarkers to guide effective targeted therapies, with biomarker-driven clinical trials for personalised medicine becoming increasingly common in several cancers. Interestingly, many of the aberrant signalling pathways in PDAC rely on downstream signal transduction through the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways, which has led to the development of several approaches to target these key regulators, primarily as combination therapies. The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway.

Item Type:Articles
Additional Information:This work was supported by an Nation Health and Medical Research (NHMRC) project grant, an NHMRC fellowship, an Nation Breast Cancer Foundation (NBCF) grant, an Australian Research Council (ARC) Future fellowship, a Len Ainsworth Pancreatic Cancer Fellowship, Cancer Council NSW grant, a Tour de Cure grant and Cancer Research UK (CRUK) core funding (A17196 and A21139). This project was made possible by an Avner Pancreatic Cancer Foundation Grant.
Glasgow Author(s) Enlighten ID:Timpson, Dr Paul and Evans, Professor Jeff and Morton, Professor Jen
Authors: Conway, J. R.W., Herrmann, D., Evans, T.R. J., Morton, J. P., and Timpson, P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Gut
Publisher:BMJ Publishing Group
ISSN (Online):1468-3288
Published Online:05 November 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Gut 68(4): 742-758
Publisher Policy:Reproduced under a Creative Commons License

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