Evidence map›Paper›PMID 30288129›Full record

ArticleClinical pharmacology : advances and applications2018

Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian adenocarcinoma with a bispecific ligand-directed toxin.

Felix Oh, Deborah Todhunter, Elizabeth Taras, Daniel A Vallera, Antonella Borgatti

Open access · goldAbstract read
In one paragraph

Article in Clinical pharmacology : advances and applications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

5 authors at 2 institutions in 1 country.

Felix OhDepartment of Therapeutic Radiology-Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA, valle001@umn.edu.
Deborah TodhunterDepartment of Therapeutic Radiology-Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA, valle001@umn.edu.
Elizabeth TarasDepartment of Therapeutic Radiology-Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA, valle001@umn.edu.
Daniel A ValleraDepartment of Therapeutic Radiology-Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA, valle001@umn.edu.
Antonella BorgattiAnimal Cancer Care and Research (ACCR) Program, University of Minnesota, St. Paul, MN, USA, valle001@umn.edu.
University of Minnesota Medical Center · USUniversity of Minnesota · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI John E. Wagner · 1995 to 2026
$48.2M
Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
Viral priming and targeting NK cells against solid tumor malignanciesR35CA197292 · NCI · UNIVERSITY OF MINNESOTA · PI MILLER, JEFFREY S. · 2015 to 2021
$6.2M
GVL TO REDUCE AML RELAPSE AFTER MURINE ALLOGENEIC BMTR01CA072669 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1997 to 2017
$4.9M
IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATIONR01CA036725 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI VALLERA, DANIEL A · 1985 to 2015
$3.3M
Preclinical evaluation and clinical translation of novel bispecific toxins that tK01OD017242 · OD · UNIVERSITY OF MINNESOTA · PI BORGATTI, ANTONELLA M · 2014 to 2018
$739k
NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA111412NCI NIH HHS R01 CA036725NCI NIH HHS R01 CA072669NCI NIH HHS R35 CA197292NIH HHS K01 OD017242
6 · The paper itself

Abstract

purposeHuman sarcomas are rare and difficult to treat cancerous tumors typically arising from soft tissue or bone. Conversely, carcinomas are the most common cancer subtype in humans and the primary cause of mortality across all cancer patients. While conventional therapeutic modalities can prolong disease-free intervals and survival in some cases, treatment of refractory or recurrent solid tumors is challenging, and tumor-related mortality remains unacceptably high. The identification of overexpressed cell surface receptors on sarcoma and carcinoma cells has provided a valuable tool to develop targeted toxins as an alternative anticancer strategy. Recent investigation of recombinant protein-linked toxins that specifically target these cancer receptors has led to the development of highly specific, cytotoxic, and deimmunized drugs that can kill cancer cells.

methodsThis study investigated a recombinant protein called epidermal growth factor bispecific angiotoxin (eBAT), which is designed to target the epidermal growth factor receptor (EGFR) on cancer cells and the urokinase plasminogen activator receptor (uPAR) on cancer cells and associated tumor vasculature. Both receptors are expressed by a variety of human sarcomas and carcinomas. Flow cytometry techniques were used to determine binding affinity of eBAT to cancer cells, and proliferation assays were performed to calculate tumor killing ability based on half-maximal inhibitory concentrations.

resultseBAT demonstrated cytotoxicity against a variety of sarcoma and carcinoma cells that overexpress EGFR and uPAR in vitro and showed greater cell killing ability and binding affinity to cancer cells compared with its monospecific counterparts.

conclusionThe results of our study are promising, and further studies will be necessary to confirm the applicability of eBAT as a supplementary therapy for a variety of sarcomas, carcinomas, and possibly other refractory malignancies that express EGFR and uPAR.

Indexed as

carcinomaeBATEGFRsarcomauPAR

Identifiers

PMID30288129
PMCPMC6163021
OpenAlexW2892781066

What OpenQuestion holds

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LicenceCC BY-NC
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.