Evidence map›Paper›PMID 29898401›Full record

ArticleCell reports2018

Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer.

James R W Conway, Sean C Warren, David Herrmann, Kendelle J Murphy, Aurélie S Cazet, Claire Vennin, Robert F Shearer, Monica J Killen, Astrid Magenau, Pauline Mélénec and 16 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
  2. Optical and Photoacoustic Imaging.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 9 institutions in 4 countries.

James R W ConwayGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Sean C WarrenGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
David HerrmannGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia.
Kendelle J MurphyGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Aurélie S CazetGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Claire VenninGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Robert F ShearerGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Monica J KillenGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Astrid MagenauGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia.
Pauline MélénecGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Mark PineseGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia.
Max NobisGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Anaiis ZaratzianGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Alice BoulghourjianGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Andrew M Da SilvaGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia.
Gonzalo Del Monte-NietoSt Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia; Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
Arne S A AdamDevelopmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
Richard P HarveySt Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia; Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2033, Australia.
Jody J HaighAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
Yingxiao WangDepartment of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
David R CroucherGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia; School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Owen J SansomCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
Marina PajicGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia.
C Elizabeth CaldonGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia.
Jennifer P MortonCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. Electronic address: j.morton@beatson.gla.ac.uk.
Paul TimpsonGarvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia. Electronic address: p.timpson@garvan.org.au.
The Kinghorn Cancer Centre · AUGarvan Institute of Medical Research · AUSt Vincent's Clinic · AUCancer Research UK · GBMonash University · AUUniversity College Dublin · IEUniversity of Glasgow · GBUniversity of Illinois Urbana-Champaign · USVictor Chang Cardiac Research Institute · AU

Funding

Integrative Bioengineering of Heart, Vessels, and BloodT32HL105373 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, INTAGLIETTA, MARCOS · 2010 to 2019
$3.6M
Cancer Research UK 21139
6 · The paper itself

Abstract

Application of advanced intravital imaging facilitates dynamic monitoring of pathway activity upon therapeutic inhibition. Here, we assess resistance to therapeutic inhibition of the PI3K pathway within the hypoxic microenvironment of pancreatic ductal adenocarcinoma (PDAC) and identify a phenomenon whereby pronounced hypoxia-induced resistance is observed for three clinically relevant inhibitors. To address this clinical problem, we have mapped tumor hypoxia by both immunofluorescence and phosphorescence lifetime imaging of oxygen-sensitive nanoparticles and demonstrate that these hypoxic regions move transiently around the tumor. To overlay this microenvironmental information with drug response, we applied a FRET biosensor for Akt activity, which is a key effector of the PI3K pathway. Performing dual intravital imaging of drug response in different tumor compartments, we demonstrate an improved drug response to a combination therapy using the dual mTORC1/2 inhibitor AZD2014 with the hypoxia-activated pro-drug TH-302.

Indexed as

Drug Resistance, NeoplasmSignal TransductionAnimalsBenzamidesCell Line, TumorDrug Therapy, CombinationFemaleFluorescence Resonance Energy TransferHumansHypoxiaIntravital MicroscopyMiceMice, Inbred BALB CMorpholinesNanoparticlesNitroimidazolesBenzamidesMorpholinesNitroimidazolesPhosphatidylinositol 3-KinasesPhosphoramide MustardsProto-Oncogene Proteins c-aktPyrimidinesTH 302vistusertibAktAZD2014FREThypoxiaintravital imagingnanoparticlespancreatic cancerPI3K pathwayPLIMpro-drug

Identifiers

PMID29898401
PMCPMC6019737
OpenAlexW2808006305

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.