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


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.

Type Journal
ISBN 0017-5749
Authors Conway, J. R.; Herrmann, D.; Evans, T. J.; Morton, J. P.; Timpson, P.
Responsible Garvan Author Prof Paul Timpson
Publisher Name GUT
Published Date 2019-04-01
Published Volume 68
Published Issue 4
Published Pages 742-758
Status Published in-print
DOI 10.1136/gutjnl-2018-316822
URL link to publisher's version