Evidence map›Paper›PMID 39821893›Full record

ReviewJournal of neuro-oncology2025

It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.

Rebeca Yakubov, Ramneet Kaloti, Phooja Persaud, Anna McCracken, Gelareh Zadeh, Severa Bunda

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

19 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  19. Phytochemical combinations of lichenFrontiers in pharmacology · 2025
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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

6 authors.

Rebeca YakubovMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
Ramneet KalotiMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
Phooja PersaudMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
Anna McCrackenMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
Gelareh ZadehMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada. gelareh.zadeh@uhn.ca.
Severa BundaMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada. severa.bunda@uhn.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to the aggressive nature of glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due to the emergence of resistance mechanisms.

objectiveThis review investigates how inhibition of the RTK/Ras/Raf/MEK/ERK pathway alters transcription factors, contributing to acquired resistance mechanisms in GBM. It also highlights the critical role of transcription factor dysregulation in therapeutic resistance. METHODS &

resultsFindings from key studies on the RTK/Ras/Raf/MEK/ERK pathway in GBM were synthesized to explore the role of transcription factor dysregulation in resistance to targeted therapies, radiation, and chemotherapy. The review highlights that transcription factors undergo significant dysregulation following RTK/Ras/Raf/MEK/ERK pathway inhibition, contributing to therapeutic resistance.

conclusionTranscription factors are promising targets for overcoming treatment resistance in GBM, with cotreatment strategies combining RTK/Ras/Raf/MEK/ERK pathway inhibitors and transcription factor-targeted therapies presenting a novel approach. Despite the challenges of targeting complex structures and interactions, advancements in drug development and precision technologies hold great potential. Continued research is essential to refine these strategies and improve outcomes for GBM and other aggressive cancers.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaMAP Kinase Signaling SystemReceptor Protein-Tyrosine KinasesAnimalsHumansraf KinasesSignal Transductionraf KinasesReceptor Protein-Tyrosine KinasesGlioblastomaResistance mechanismsRTK/Raf/MEK/ERK inhibitorsTranscription factors

Identifiers

PMID39821893
PMCPMC11937199

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.