SynthesisClinical cancer research : an official journal of the American Association for Cancer Research2024
ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis.
Synthesis in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03233152 (A Phase I/II Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma), which is not on this map. Cited by 12 papers.
What it found
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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.
A Phase I/II Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma
Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Glioma-intrinsic MAPK/ERK signaling promotes immunotherapy efficacy through T cell infiltration and interferon responses.Nature communications · 2026Article
- Mapping kinase-dependent tumor immune adaptation with multiplexed single-cell CRISPR screens.bioRxiv : the preprint server for biology · 2026Article
- Biomarkers for predicting immunotherapy response and resistance in glioblastoma.Frontiers in immunology · 2026Review
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?Neuro-oncology · 2025Review
- Review
- Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood-brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas.Neuro-oncology · 2024Article
- MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy.bioRxiv : the preprint server for biology · 2024Article
- NKG2C/Journal for immunotherapy of cancer · 2024Article
- A Synopsis of Biomarkers in Glioblastoma: Past and Present.Current issues in molecular biology · 2024Review
- Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.Nature communications · 2024Article
- Molecular diversity in isocitrate dehydrogenase-wild-type glioblastoma.Brain communications · 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
19 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeEvidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts. EXPERIMENTAL
designIn a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and OS. Patients received intravenous nivolumab, followed by maximal safe resection and an intracerebral injection of either ipilimumab alone or combined with nivolumab. Biweekly adjuvant nivolumab was then administered up to five times (NCT03233152). Using REporting recommendations for tumor MARKER prognostic studies (REMARK) criteria, we conducted independent analyses for p-ERK quantification and statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models and meta-analysis were employed to assess p-ERK as a predictive biomarker after immunotherapy.
resultsLower median p-ERK+ cell density was observed compared with prior studies, likely due to variable tissue processing across cohorts. Nonetheless, high p-ERK was associated with prolonged OS, particularly in isocitrate dehydrogenase wild-type glioblastomas (P = 0.036). Median OS for high and low p-ERK patients were 55.6 and 30 weeks, respectively. Multivariable analysis reinforced p-ERK's significance in survival prediction (P = 0.011). Upon p-ERK normalization across cohorts (n = 65), meta-analysis supported the survival benefit of elevated tumor p-ERK levels (P = 0.0424).
conclusionsThis study strengthens the role of p-ERK as a predictive biomarker for OS in patients with glioblastoma on immune checkpoint blockade. Future research should focus on further validation in prospective trials and the standardization of preanalytical variables influencing p-ERK quantification.
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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.