Navigating glioblastoma therapy: A narrative review of emerging immunotherapeutics and small-molecule inhibitors

Abstract

Glioblastoma multiforme (GBM) is the most common malignant primary tumor of the central nervous system (CNS), accounting for the majority of brain tissue tumors and CNS neoplasms. GBM has an incidence rate of 3.2/100,000 people in the United States, with an abysmal survival rate of 15 months with treatment and under 3 months for untreated patients. GBM remains incurable, with no disease-modifying treatment available. As a grade IV astrocytoma, GBM is highly aggressive, characterized by rapid proliferation, high metabolic demands, substantial angiogenesis, and diffuse infiltration of healthy parenchyma. The GBM genome is highly heterogeneous, with unpredictable amplification patterns, dysregulation, and mutational activation of receptor tyrosine kinase genes, tumor suppressor genes, and growth factor signaling. GBM’s indistinct tumor margins, its highly adaptive interaction with the brain microenvironment, and the existence of the blood-brain barrier and the blood-brain tumor barrier further limit effective anti-GBM therapeutic strategies. Hence, anti-GBM drug discoveries and molecular techniques that aim for patient-specific treatment stratification are of profound clinical and therapeutic significance. The current paper aims to outline the fundamental pathophysiology, tumorigenicity, and immunosuppressive mechanism of GBMs, review current treatment options for GBMs, and examine the contemporary challenges and advances in anti-GBM drug discovery and delivery. Finally, the paper aims to shed light on the emergence of small-molecule inhibitors, immune checkpoint inhibitors, and vaccination therapy as potentially efficacious therapeutic strategies for treating GBM.

Keywords

Glioblastoma multiforme / Immunotherapy / Checkpoint inhibitors / Anti-GBM therapeutic strategies / Immunosuppressive mechanism / Small-molecule inhibitors

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