Evidence map›Paper›PMID 26750997›Full record

ArticlemAbs2016

Incomplete target neutralization by the anti-cancer antibody rilotumumab.

Sameer A Greenall, Timothy E Adams, Terrance G Johns

Abstract read
In one paragraph

Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Targeting HGF/c-MET Axis in Pancreatic Cancer.International journal of molecular sciences · 2020
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
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

3 authors.

Sameer A Greenalla Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Centre for Cancer Research, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton , VIC 3168 , Australia.
Timothy E Adamsc Biomedical Manufacturing Program, Commonwealth Scientific and Industrial Research Organisation , 343 Royal Parade, Parkville , VIC 3052 , Australia.
Terrance G Johnsa Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Centre for Cancer Research, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton , VIC 3168 , Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The antibody rilotumumab, which has been tested in multiple Phase 2 and Phase 3 trials, has been reported to neutralize hepatocyte growth factor (HGF), the ligand for the oncogene MET. However, we report that rilotumumab does not prevent HGF from directly binding to MET on conventional and primary patient-derived human gliomasphere lines, a trait driven by the HGF α-chain, which remains free to engage cell-surface glycosaminoglycans and the receptor MET. This binding induces MET phosphorylation, initiates robust AKT and ERK signaling and potentiates biological effects such as cell scattering. This partial antagonism was highly exacerbated in the presence of activated epidermal growth factor receptor, which is common in several cancers. Hence, we confirm that rilotumumab is only a partial antagonist of HGF activity, a finding that has considerable implications for the therapeutic use of rilotumumab.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingCell Line, TumorClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicGlycosaminoglycansHepatocyte Growth FactorHumansMAP Kinase Signaling SystemPhosphorylationProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingglucosaminoglycansGlycosaminoglycansHepatocyte Growth FactorHGF protein, humanMET protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metrilotumumabCancerEGFRHGFMETtargeted therapy

Identifiers

PMID26750997
PMCPMC4966628

What OpenQuestion holds

Textmetadata
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.