Evidence map›Paper›PMID 36672409›Full record

ArticleCancers2023

Rilotumumab Resistance Acquired by Intracrine Hepatocyte Growth Factor Signaling.

Fabiola Cecchi, Karen Rex, Joanna Schmidt, Cathy D Vocke, Young H Lee, Sandra Burkett, Daniel Baker, Michael A Damore, Angela Coxon, Teresa L Burgess and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
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 at 2 institutions in 1 country.

Fabiola CecchiUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Karen RexAmgen, Inc., Thousand Oaks, CA 91320, USA.
Joanna SchmidtAmgen, Inc., Thousand Oaks, CA 91320, USA.
Cathy D VockeUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9256-7607
Young H LeeUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sandra BurkettMolecular Cytogenetics Core Facility, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.ORCID 0000-0002-5476-4028
Daniel BakerAmgen, Inc., Thousand Oaks, CA 91320, USA.
Michael A DamoreAmgen, Inc., Thousand Oaks, CA 91320, USA.
Angela CoxonAmgen, Inc., Thousand Oaks, CA 91320, USA.
Teresa L BurgessAmgen, Inc., Thousand Oaks, CA 91320, USA.
Donald P BottaroUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-5057-5334
Amgen (United States) · USNational Institutes of Health · US

Funding

Tissue ProcessingSequencing FacilityZICBC011044 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI VOCKE, CATHY D · 2009 to 2025
$13.5M
Oncogenic Met Signaling in Urologic MalignanciesZIABC011124 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BOTTARO, DONALD · 2009 to 2021
$5.8M
Intramural NIH HHS ZIA BC011124NCI NIH HHS ZIA BC011124
6 · The paper itself

Abstract

Drug resistance is a long-standing impediment to effective systemic cancer therapy and acquired drug resistance is a growing problem for molecularly-targeted therapeutics that otherwise have shown unprecedented successes in disease control. The hepatocyte growth factor (HGF)/Met receptor pathway signaling is frequently involved in cancer and has been a subject of targeted drug development for nearly 30 years. To anticipate and study specific resistance mechanisms associated with targeting this pathway, we engineered resistance to the HGF-neutralizing antibody rilotumumab in glioblastoma cells harboring autocrine HGF/Met signaling, a frequent abnormality of this brain cancer in humans. We found that rilotumumab resistance was acquired through an unusual mechanism comprising dramatic HGF overproduction and misfolding, endoplasmic reticulum (ER) stress-response signaling and redirected vesicular trafficking that effectively sequestered rilotumumab and misfolded HGF from native HGF and activated Met. Amplification of

Indexed as

acquired drug resistanceglioblastomahepatocyte growth factorMetrilotumumab

Identifiers

PMID36672409
PMCPMC9857108
OpenAlexW4315628375

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.