Evidence map›Paper›PMID 32635473›Full record

ArticleCancers2020

Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells.

Timothy P Cash, Sonia Alcalá, María Del Rosario Rico-Ferreira, Elena Hernández-Encinas, Jennifer García, María Isabel Albarrán, Sandra Valle, Javier Muñoz, Sonia Martínez-González, Carmen Blanco-Aparicio and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. TargetingInternational journal of molecular sciences · 2020
    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

13 authors at 4 institutions in 1 country.

Timothy P CashTumor Suppression Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Sonia AlcaláDepartment of Cancer Biology, Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM), 28029 Madrid, Spain.
María Del Rosario Rico-FerreiraExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Elena Hernández-EncinasExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Jennifer GarcíaExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
María Isabel AlbarránExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Sandra ValleDepartment of Cancer Biology, Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM), 28029 Madrid, Spain.ORCID 0000-0002-7555-9357
Javier MuñozProteomics Unit-ProteoRed-Instituto de Salud Carlos III, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Sonia Martínez-GonzálezExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.ORCID 0000-0003-2230-7794
Carmen Blanco-AparicioExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.ORCID 0000-0002-3249-6595
Joaquín PastorExperimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Manuel SerranoTumor Suppression Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.ORCID 0000-0001-7177-9312
Bruno SainzDepartment of Cancer Biology, Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM), 28029 Madrid, Spain.
Spanish National Cancer Research Centre · ESInstituto de Investigaciones Biomédicas Sols-Morreale · ESInstitució Catalana de Recerca i Estudis Avançats · ESInstituto de Salud Carlos III · ES

Funding

European Research Council ERC-2014-AdG/669622Fero Foundation n/aFundación Científica Asociación Española Contra el Cáncer GC16173694BARBInstituto de Salud Carlos III PI15/01507Instituto de Salud Carlos III PI18/00757La Caixa Foundation n/aMinisterio de Ciencia, Innovación y Universidades SAF2017-82613-RMinisterio de Economía y Competitividad RYC-2012-12104
6 · The paper itself

Abstract

Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC.

Indexed as

cancer stem cellscompound librarylysosomal membrane permeabilizationpancreatic ductal adenocarcinomapatient-derived xenografts

Identifiers

PMID32635473
PMCPMC7407272
OpenAlexW3039961652

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.