Evidence map›Paper›PMID 34571996›Full record

ReviewCells2021

Strategic Development of an Immunotoxin for the Treatment of Glioblastoma and Other Tumours Expressing the Calcitonin Receptor.

Pragya Gupta, David L Hare, Peter J Wookey

Open access · goldAbstract readReview
In one paragraph

Review in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 49% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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 at 1 institution in 1 country.

Pragya GuptaDepartment of Medicine-Austin, University of Melbourne, Heidelberg 3084, Australia.ORCID 0000-0001-8617-0817
David L HareDepartment of Medicine-Austin, University of Melbourne, Heidelberg 3084, Australia.
Peter J WookeyDepartment of Medicine-Austin, University of Melbourne, Heidelberg 3084, Australia.
The University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

New strategies aimed at treatment of glioblastoma are frequently proposed to overcome poor prognosis. Recently, research has focused on glioma stem cells (GSCs), some quiescent, which drive expansion of glioblastoma and provide the complexity and heterogeneity of the tumour hierarchy. Targeting quiescent GSCs is beyond the capability of conventional drugs such as temozolomide. Here, we discuss the proposal that the calcitonin receptor (CT Receptor), expressed in 76-86% of patient biopsies, is expressed by both malignant glioma cells and GSCs. Forty-two percent (42%) of high-grade glioma (HGG; representative of GSCs) cell lines available from one source express CT Receptor protein in cell culture. The pharmacological calcitonin (CT)-response profiles of four of the HGG cell lines were reported, suggesting mutational/splicing inactivation. Alternative splicing, commonly associated with cancer cells, could result in the predominant expression of the insert-positive isoform and explain the atypical pharmacology exhibited by CT non-responders. A role for the CT Receptor as a putative tumour suppressor and/or oncoprotein is discussed. Both CT responders and non-responders were sensitive to immunotoxins based on an anti-CT Receptor antibody conjugated to ribosomal-inactivating proteins. Sensitivity was increased by several logs with the triterpene glycoside SO1861, an endosomal escape enhancer. Under these conditions, the immunotoxins were 250-300 times more potent than an equivalent antibody conjugated with monomethyl auristatin E. Further refinements for improving the penetration of solid tumours are discussed. With this knowledge, a potential strategy for effective targeting of CSCs expressing this receptor is proposed for the treatment of GBM.

Indexed as

AnimalsBrain NeoplasmsGlioblastomaGliomaHumansImmunotoxinsNeoplastic Stem CellsReceptors, CalcitoninImmunotoxinsReceptors, Calcitoninantibodybrain tumourcalcitonin receptorCT Receptorglioblastomaglioma stem cellsG protein-coupled receptor

Identifiers

PMID34571996
PMCPMC8466289
OpenAlexW3197634489

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.