Evidence map›Paper›PMID 37983271›Full record

ArticlePLoS computational biology2023

Overcoming chemotherapy resistance in low-grade gliomas: A computational approach.

Thibault Delobel, Luis E Ayala-Hernández, Jesús J Bosque, Julián Pérez-Beteta, Salvador Chulián, Manuel García-Ferrer, Pilar Piñero, Philippe Schucht, Michael Murek, Víctor M Pérez-García

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. In Silico Clinical Trials in Drug Development: A Systematic Review.Therapeutic innovation & regulatory science · 2026
    Pooled it
  2. Review
  3. Artificial intelligence in neuro-oncology: methodological bases, practical applications and ethical and regulatory issues.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
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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

10 authors at 6 institutions in 4 countries.

Thibault DelobelDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0003-3993-9691
Luis E Ayala-HernándezDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0002-5383-5058
Jesús J BosqueDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0002-9116-1453
Julián Pérez-BetetaDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0003-0317-6215
Salvador ChuliánDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0001-5509-5236
Manuel García-FerrerDepartment of Radiology, Virgen del Rocío University Hospital, Seville, Spain.
Pilar PiñeroDepartment of Radiology, Virgen del Rocío University Hospital, Seville, Spain.
Philippe SchuchtDepartment of Neurosurgery, Inselspital Bern and University Hospital, Bern, Switzerland.
Michael MurekDepartment of Neurosurgery, Inselspital Bern and University Hospital, Bern, Switzerland.
Víctor M Pérez-GarcíaDepartment of Mathematics, Mathematical Oncology Laboratory (MOLAB), University of Castilla-La Mancha, Ciudad Real, Spain.ORCID 0000-0002-6575-495X
University of Castilla-La Mancha · ESHospital Universitario Virgen del Rocío · ESUniversity Hospital of Bern · CHSorbonne Université · FRUniversidad de Cádiz · ESUniversidad de Guadalajara · MX

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.

Indexed as

Brain NeoplasmsGliomaAntineoplastic Agents, AlkylatingDacarbazineHumansTemozolomideAntineoplastic Agents, AlkylatingDacarbazineTemozolomide

Identifiers

PMID37983271
PMCPMC10695391
OpenAlexW4388822362

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.