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Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine
  1. James RW Conway1,
  2. David Herrmann1,2,
  3. TR Jeffry Evans3,4,
  4. Jennifer P Morton3,4,
  5. Paul Timpson1,2
  1. 1 Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Cancer Division, Sydney, New South Wales, Australia
  2. 2 St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
  3. 3 Cancer Department, Cancer Research UK Beatson Institute, Glasgow, UK
  4. 4 Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Paul Timpson, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; p.timpson{at}garvan.org.au

Abstract

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.

  • pancreatic cancer
  • clinical trials
  • cell biology

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Footnotes

  • Contributors JRWC and PT developed the main concept of the manuscript. All authors wrote the manuscript. JPM and PT wrote grant applications that funded the work.

  • Funding 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.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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