ArticleNeuro-oncology2024
Dual p38MAPK and MEK inhibition disrupts adaptive chemoresistance in mesenchymal glioblastoma to temozolomide.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- TET1 Inhibition Promotes Therapeutic Sensitivity in TP53-Mutant GBM by Influencing Genome Fragility and Altering TAMs Biology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel cilengitide derivatives suppress migration and invasion of temozolomide-resistant glioblastoma cells via MAPK/Akt pathway inhibition.Journal of neuro-oncology · 2026Article
- Sphingolipid-associated signature unveils TIMP1-driven temozolomide resistance and guides stratified therapy in glioblastoma.Frontiers in immunology · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- Glioportal: a comprehensive transcriptomic resource unveiling ligand-mediated mesenchymal transition in glioblastoma.Neuro-oncology · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- The multifaceted therapeutical role of low-density lipoprotein receptor family in high-grade glioma.Molecular oncology · 2024Review
- Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.Biomedicines · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPrecision treatment of glioblastoma is increasingly focused on molecular subtyping, with the mesenchymal subtype particularly resistant to temozolomide. Here, we aim to develop a targeted therapy for temozolomide resensitization in the mesenchymal subtype.
methodsWe integrated kinomic profiles and kinase inhibitor screens from patient-derived proneural and mesenchymal glioma-propagating cells and public clinical datasets to identify key protein kinases implicated in temozolomide resistance. RNAseq, apoptosis assays, and comet assays were used to examine the role of p38MAPK signaling and adaptive chemoresistance in mesenchymal cells. The efficacy of dual p38MAPK and MEK/ERK inhibition using ralimetinib (selective orally active p38MAPK inhibitor; phase I/II for glioblastoma) and binimetinib (approved MEK1/2 inhibitor for melanoma; phase II for high-grade glioma) in primary and recurrent mesenchymal tumors was evaluated using an intracranial patient-derived tumor xenograft model, focusing on survival analysis.
resultsOur transcriptomic-kinomic integrative analysis revealed p38MAPK as the prime target whose gene signature enables patient stratification based on their molecular subtypes and provides prognostic value. Repurposed p38MAPK inhibitors synergize favorably with temozolomide to promote intracellular retention of temozolomide and exacerbate DNA damage. Mesenchymal cells exhibit adaptive chemoresistance to p38MAPK inhibition through a pH-/calcium-mediated MEK/ERK pathway. Dual p38MAPK and MEK inhibition effectively maintain temozolomide sensitivity in primary and recurrent intracranial mesenchymal glioblastoma xenografts.
conclusionsTemozolomide resistance in mesenchymal glioblastoma is associated with p38MAPK activation. Adaptive chemoresistance in p38MAPK-resistant cells is mediated by MEK/ERK signaling. Adjuvant therapy with dual p38MAPK and MEK inhibition prolongs temozolomide sensitivity, which can be developed into a precision therapy for the mesenchymal subtype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.