Emerging therapies for glioblastoma: current state and future directions.

Authors: Rong L, Li N, Zhang Z

Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given the poor survival with currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment in basic science of glioblastoma are rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling of glioblastoma as well as the brain microenvironment and immune system interactions. Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. In addition, techniques to overcome the blood-brain barrier (BBB) for targeted delivery are being tested in clinical trials in patients with recurrent GBM. Here, we set forth the rationales for these promising therapies in treating GBM, review the potential novel agents, the current status of preclinical and clinical trials, and discuss the challenges and future perspectives in glioblastoma immuno-oncology.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review and synthesize the rationale, current status, and future prospects of immunotherapy and targeted delivery strategies for treating glioblastoma.

Disease model Glioblastoma

Outcomes and Safety

Summary of Outcomes Immunotherapy modalities (checkpoint blockade, CAR T, oncolytic viruses, vaccines, BiTEs) are generally safe and can induce pro‑inflammatory/antitumor responses in preclinical and early‑phase studies but have shown limited, inconsistent clinical efficacy in glioblastoma due to local immunosuppression, antigen heterogeneity/escape, and BBB barriers, supporting the need for combinatorial and personalized approaches. No focused ultrasound parameters were tested or reported in this paper.

Safety-related matter The paper notes that immunotherapy has demonstrated safety and feasibility in a variety of malignancies but its efficacy in GBM remains unproven; it raises concerns about chronic immune toxicities, long-term implications, and other potential side effects and urges strategies to prevent and minimize adverse events. The authors do not report specific GBM trial data showing absence of adverse effects.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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