Evidence map›Paper›PMID 38534332›Full record

ArticleCells2024

Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling.

Mariangela Morelli, Francesca Lessi, Sara Franceschi, Gianmarco Ferri, Manuel Giacomarra, Michele Menicagli, Carlo Gambacciani, Francesco Pieri, Francesco Pasqualetti, Nicola Montemurro and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2024. 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
1.3field-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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  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

14 authors at 3 institutions in 1 country.

Mariangela MorelliFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.ORCID 0000-0001-8796-4037
Francesca LessiFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.ORCID 0000-0002-3346-4296
Sara FranceschiFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.ORCID 0000-0002-4246-4407
Gianmarco FerriFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.
Manuel GiacomarraFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.
Michele MenicagliFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.
Carlo GambaccianiNeurosurgical Department of Spedali Riuniti di Livorno, 57124 Livorno, Italy.
Francesco PieriNeurosurgical Department of Spedali Riuniti di Livorno, 57124 Livorno, Italy.
Francesco PasqualettiRadiotherapy Department, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy.ORCID 0000-0002-0788-1205
Nicola MontemurroDepartment of Neurosurgery, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy.ORCID 0000-0002-3686-8907
Paolo AretiniFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.ORCID 0000-0003-1075-4319
Orazio Santo SantonocitoNeurosurgical Department of Spedali Riuniti di Livorno, 57124 Livorno, Italy.
Anna Luisa Di StefanoNeurosurgical Department of Spedali Riuniti di Livorno, 57124 Livorno, Italy.
Chiara Maria MazzantiFondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.ORCID 0000-0002-7249-9221
Fondazione Pisa · ITOspedale di Livorno · ITAzienda Ospedaliera Universitaria Pisana · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients' resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response.

Indexed as

GlioblastomaPhenylurea CompoundsPyridinesAntineoplastic Agents, AlkylatingHumansNeoplasm Recurrence, LocalTemozolomideAntineoplastic Agents, AlkylatingPhenylurea CompoundsPyridinesregorafenibTemozolomidedrug responseglioblastomaNADP(H) FLIMorganoidsRegorafenib

Identifiers

PMID38534332
PMCPMC10968984
OpenAlexW4392658072

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.