Evidence map›Paper›PMID 26766740›Full record

ArticleBritish journal of cancer2016

Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer.

Srinivasa P Pothula, Zhihong Xu, David Goldstein, Andrew V Biankin, Romano C Pirola, Jeremy S Wilson, Minoti V Apte

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

Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

56 citing papers in PubMed, 93 citations in OpenAlex.

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  9. Nuclear Galectin-1 promotesProceedings of the National Academy of Sciences of the United States of America · 2025
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  19. Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023
    Review
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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

7 authors at 4 institutions in 1 country.

Srinivasa P PothulaPancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Zhihong XuPancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
David GoldsteinDepartment of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Andrew V BiankinCancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Romano C PirolaPancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Jeremy S WilsonPancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Minoti V AptePancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
UNSW Sydney · AUIngham Institute · AUGarvan Institute of Medical Research · AUPrince of Wales Hospital · AU

Funding

Cancer Research UK 17263Chief Scientist Office SGP/1Medical Research Council MC_PC_15080
6 · The paper itself

Abstract

backgroundPancreatic stellate cells (PSCs, which produce the stroma of pancreatic cancer (PC)) interact with cancer cells to facilitate PC growth. A candidate growth factor pathway that may mediate this interaction is the HGF-c-MET pathway.

methodsEffects of HGF inhibition (using a neutralising antibody AMG102) alone or in combination with gemcitabine were assessed (i) in vivo using an orthotopic model of PC, and (ii) in vitro using cultured PC cells (AsPC-1) and human PSCs.

resultsWe have shown that human PSCs (hPSCs) secrete HGF but do not express the receptor c-MET, which is present predominantly on cancer cells. HGF inhibition was as effective as standard chemotherapy in inhibiting local tumour growth but was significantly more effective than gemcitabine in reducing tumour angiogenesis and metastasis. HGF inhibition has resulted in reduced metastasis; however, interestingly this antimetastatic effect was lost when combined with gemcitabine. This suggests that gemcitabine treatment selects out a subpopulation of cancer cells with increased epithelial-mesenchymal transition (EMT) and stem-cell characteristics, as supported by our findings of increased expression of EMT and stem-cell markers in tumour sections from our animal model. In vitro studies showed that hPSC secretions induced proliferation and migration, but inhibited apoptosis, of cancer cells. These effects were countered by pretreatment of hPSC secretions with a HGF-neutralising antibody but not by gemcitabine, indicating a key role for HGF in PSC-PC interactions.

conclusionsOur studies suggest that targeted therapy to inhibit stromal-tumour interactions mediated by the HGF-c-MET pathway may represent a novel therapeutic approach in PC that will require careful modelling for optimal integration with existing treatment modalities.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementCell ProliferationDeoxycytidineEpithelial-Mesenchymal TransitionGemcitabineHepatocyte Growth FactorHumansIn Vitro TechniquesMiceAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsDeoxycytidineGemcitabineHepatocyte Growth FactorHGF protein, humanMET protein, humanProto-Oncogene Proteins c-metrilotumumab

Identifiers

PMID26766740
PMCPMC4742591
OpenAlexW2282442963

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.