Evidence map›Paper›PMID 34877810›Full record

ArticlePhysiological reports2021

AXL targeting by a specific small molecule or monoclonal antibody inhibits renal cell carcinoma progression in an orthotopic mice model.

Tony J Chen, Piotr Mydel, Małgorzata Benedyk-Machaczka, Marta Kamińska, Urszula Kalucka, Magnus Blø, Jessica Furriol, Gro Gausdal, James Lorens, Tarig Osman and 1 more

Abstract read
In one paragraph

Article in Physiological reports, 2021. 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. Article
  2. Article
  3. Article
  4. AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025
    Review
  5. Article
  6. Review
  7. AXL Inhibitors: Status of Clinical Development.Current oncology reports · 2023
    Review
  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

11 authors.

Tony J ChenDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.ORCID 0000-0002-7298-5529
Piotr MydelDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Małgorzata Benedyk-MachaczkaDepartment of Microbiology, Jagiellonian University, Krakow, Poland.
Marta KamińskaDepartment of Microbiology, Jagiellonian University, Krakow, Poland.
Urszula KaluckaDepartment of Microbiology, Jagiellonian University, Krakow, Poland.
Magnus BløBerGenBio ASA, Bergen, Norway.
Jessica FurriolDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Gro GausdalBerGenBio ASA, Bergen, Norway.
James LorensDepartment of Biomedicine, Centre for Cancer Biomarkers, Norwegian Centre of Excellence, University of Bergen, Bergen, Norway.
Tarig OsmanDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Hans-Peter MartiDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

AXL tyrosine kinase activation enhances cancer cell survival, migration, invasiveness, and promotes drug resistance. AXL overexpression is typically detected in a high percentage of renal cell carcinomas (RCCs) and is strongly associated with poor prognosis. Therefore, AXL inhibition represents an attractive treatment option in these cancers. In this preclinical study, we investigated the antitumor role of a highly selective small molecule AXL inhibitor bemcentinib (BGB324, BerGenBio), and a newly developed humanized anti-AXL monoclonal function blocking antibody tilvestamab, (BGB149, BerGenBio), in vitro and an orthotopic RCC mice model. The 786-0-Luc human RCC cells showed high AXL expression. Both bemcentinib and tilvestamab significantly inhibited AXL activation induced by Gas6 stimulation in vitro. Furthermore, tilvestamab inhibited the downstream AKT phosphorylation in these cells. The 786-0-Luc human RCC cells generated tumors with high Ki67 and vimentin expression upon orthotopic implantation in athymic BALB/c nude mice. Most importantly, both bemcentinib and tilvestamab inhibited the progression of tumors induced by the orthotopically implanted 786-0 RCC cells. Remarkably, their in vivo antitumor effectiveness was not significantly enhanced by concomitant administration of a multi-target tyrosine kinase inhibitor. Bemcentinib and tilvestamab qualify as compounds of potentially high clinical interest in AXL overexpressing RCC.

Indexed as

AnimalsAxl Receptor Tyrosine KinaseBenzocycloheptenesCarcinoma, Renal CellCell Line, TumorCell ProliferationDisease Models, AnimalDisease ProgressionHumansKidney NeoplasmsMicePhosphorylationProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesAxl Receptor Tyrosine KinasebemcentinibBenzocycloheptenesProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesTriazolesbemcentiniborthotopic RCCtilvestamab

Identifiers

PMID34877810
PMCPMC8652404

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Registered trials

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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.