# Advanced Neuroimaging and Emerging Systemic Therapies in Glioblastoma: Current Evidence and Future Directions

**Authors:** Ilona Bar-Letkiewicz, Anna Pieczyńska, Małgorzata Dudzic, Michał Szkudlarek, Krystyna Adamska, Katarzyna Hojan

PMC · DOI: 10.3390/biomedicines13112597 · 2025-10-23

## TL;DR

This review discusses current neuroimaging techniques and systemic therapies for glioblastoma, highlighting innovations and future directions to improve patient outcomes.

## Contribution

The paper provides a comprehensive overview of emerging neuroimaging and therapeutic approaches in glioblastoma treatment.

## Key findings

- Multiparametric MRI and novel PET tracers, combined with AI, improve tumor delineation and treatment prediction.
- MGMT promoter methylation status influences the effectiveness of temozolomide-based chemoradiotherapy.
- Immune checkpoint inhibitors have not improved survival in unselected glioblastoma patients.

## Abstract

Despite technological progress, glioblastoma (GBM) continues to confer dismal prognoses. Modern neuroimaging methods are assuming an ever greater role in diagnosing and monitoring brain tumors. This review shows current neuroimaging approaches and systemic therapeutic strategies for glioblastoma, with a focus on emerging and innovative treatments. Advances in multiparametric magnetic resonance imaging—MRI (diffusion, perfusion, and spectroscopy) and novel positron emission tomography (PET) tracers, complemented by radiomics and artificial intelligence (AI), now refine tumor delineation, differentiate progression from treatment effects, and may help predict treatment responses. Maximal safe resection followed by chemoradiotherapy with temozolomide remains the standard, with the greatest benefit seen in O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. Bevacizumab and other targeted modalities offer mainly progression-free, not overall survival, gains. Immune checkpoint inhibitors (e.g., nivolumab) have not improved survival in unselected GBM, while early multi-antigen CAR-T (chimeric antigen receptor T-cell) strategies show preliminary bioactivity without established durability. While actionable alterations (NTRK fusions and BRAF V600E) justify selective targeted therapy trials, their definitive benefit in classical GBM is unproven. Future priorities include harmonized imaging molecular integration, AI-driven prognostic modeling, novel PET tracers, and strategies to breach or transiently open the blood–brain barrier to enhance drug delivery. Convergence of these domains may convert diagnostic precision into improved patient outcomes.

## Linked entities

- **Genes:** MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673]
- **Chemicals:** temozolomide (PubChem CID 5394)
- **Diseases:** glioblastoma (MONDO:0018177), GBM (MONDO:0018177)

## Full-text entities

- **Genes:** BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255]
- **Diseases:** GBM (MESH:D005909), brain tumors (MESH:D001932), tumor (MESH:D009369)
- **Chemicals:** temozolomide (MESH:D000077204), nivolumab (MESH:D000077594), Bevacizumab (MESH:D000068258)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** V600E

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Source: https://tomesphere.com/paper/PMC12650646