Glioma
Glioma is a term encompassing a diverse group of primary brain tumors that arise from glial cells, which provide structural and metabolic support to neurons within the central nervous system. The pathogenesis of glioma involves the malignant transformation of astrocytes, oligodendrocytes, or ependymal cells, driven by genetic and epigenetic alterations that disrupt normal cell cycle regulation, apoptosis, and differentiation. Key molecular events often include mutations in genes such as IDH1/2, TP53, ATRX, and alterations in signaling pathways like RTK/RAS/PI3K. These tumors are characterized by diffuse infiltration into surrounding brain tissue, making complete surgical resection challenging and contributing to high recurrence rates. Gliomas exert profound health impacts, including neurological deficits, seizures, cognitive dysfunction, and increased intracranial pressure, depending on their location, size, and aggressiveness. High-grade gliomas, particularly glioblastoma, are associated with poor prognosis and significant morbidity and mortality, while lower-grade tumors may follow a more indolent course but still carry the risk of malignant progression.
Glioblastoma is the most aggressive and common form of malignant primary brain tumor in adults, classified as WHO grade IV. It is characterized by rapid proliferation, extensive infiltration, necrosis, microvascular proliferation, and marked genetic heterogeneity. Glioblastomas frequently harbor mutations in TERT promoter, EGFR amplification, and loss of heterozygosity on chromosome 10q. Clinically, GBM presents with rapidly progressive neurological symptoms and has a median survival of approximately 15 months despite aggressive therapy.
Astrocytoma arises from astrocytes and encompasses a spectrum of tumors ranging from low-grade (WHO grade I and II) to high-grade (anaplastic astrocytoma, grade III). Low-grade astrocytomas grow slowly and are more common in children and young adults, often associated with IDH mutations, while higher-grade forms exhibit increased mitotic activity, nuclear atypia, and a propensity for malignant transformation.
Oligodendroglioma originates from oligodendrocytes and is typically characterized by the presence of 1p/19q co-deletion and IDH mutations, which confer a more favorable prognosis and better response to chemoradiation. These tumors are generally slow-growing (WHO grade II or III), often presenting with seizures, and occur predominantly in adults.
Ependymoma develops from ependymal cells lining the ventricular system of the brain and the central canal of the spinal cord. These tumors can occur at any age but are more common in children, especially in the posterior fossa. Ependymomas exhibit a variable clinical course depending on grade and location, with some subtypes demonstrating a tendency for cerebrospinal fluid dissemination.
Diffuse midline glioma, including those with H3 K27M mutation, predominantly affects children and young adults. These highly infiltrative tumors typically arise in midline structures such as the thalamus, brainstem, or spinal cord. They are classified as WHO grade IV due to their aggressive behavior and poor prognosis, with median survival often less than one year.
Gliomas account for approximately 27% of all primary brain and central nervous system tumors and about 80% of malignant brain tumors. The annual incidence of glioma is estimated at 5 to 8 cases per 100,000 population worldwide, with higher rates observed in North America and Northern Europe. Glioblastoma represents the most common subtype, comprising around 45-50% of all gliomas. The incidence of gliomas increases with age, peaking between 45 and 75 years, although certain subtypes such as diffuse midline glioma are more prevalent in pediatric populations. Males are affected more frequently than females, with a male-to-female ratio of approximately 1.3:1. Risk factors include ionizing radiation exposure and rare hereditary syndromes such as Li-Fraumeni and neurofibromatosis type 1, but most cases are sporadic. Despite advances in therapy, the prognosis for high-grade gliomas remains poor, with five-year survival rates below 10% for glioblastoma, while lower-grade gliomas have more favorable outcomes but can progress to higher grades over time.
The diagnosis of glioma involves a combination of clinical evaluation, neuroimaging, histopathological examination, and molecular testing. Patients typically present with symptoms such as headaches, seizures, focal neurological deficits, or cognitive changes. Magnetic resonance imaging (MRI) with contrast is the imaging modality of choice, providing detailed information on tumor location, size, infiltration, and enhancement patterns. Advanced MRI techniques, including perfusion, diffusion, and spectroscopy, may further characterize tumor biology. Definitive diagnosis requires histopathological assessment of tumor tissue obtained via stereotactic biopsy or surgical resection. Pathological analysis determines tumor type, grade, and morphological features, while integrated molecular testing, including assessment of IDH mutation status, 1p/19q co-deletion, MGMT promoter methylation, and H3 K27M mutation, refines classification and informs prognosis and therapeutic decisions. The World Health Organization (WHO) classification system is used to grade gliomas based on histological and molecular parameters. Additional diagnostic workup may include cerebrospinal fluid analysis in select cases and functional imaging to assess involvement of eloquent brain areas.
Tovorafenib is utilized in the therapeutic management of glioma, targeting specific molecular pathways implicated in tumor growth. Bevacizumab is an anti-angiogenic monoclonal antibody that is administered to inhibit vascular endothelial growth factor (VEGF), thereby reducing tumor-associated neovascularization and edema; several biosimilar formulations, including bevacizumab-bvzr, bevacizumab-awwb, and bevacizumab-nwgd, are also available and are employed with similar indications. Teserpaturev is a treatment option that acts through mechanisms relevant to glioma pathology. Dabrafenib mesylate is prescribed as a targeted therapy for glioma patients harboring BRAF V600 mutations, functioning as a selective inhibitor of the mutated BRAF kinase. Trametinib dimethyl sulfoxide is indicated for use in combination with other agents, such as dabrafenib, to inhibit MEK1/2 kinases in the MAPK pathway, thereby providing a synergistic effect in the treatment of BRAF-mutated gliomas. These agents are integrated into individualized treatment protocols according to molecular and clinical characteristics of the tumor.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
 | tovorafenib (Rec INN; USAN) | 1096708-71-2 | C17 H12 Cl2 F3 N7 O2 S | 506.289 |
| bevacizumab | ||||
| teserpaturev (Prop INN) | 1802360-34-4 | |||
| bevacizumab; bevacizumab-bvzr | ||||
| bevacizumab; bevacizumab-awwb | ||||
| bevacizumab; bevacizumab-nwgd | ||||
 | dabrafenib mesylate (Prop INNM; USAN) | 1195765-45-7 (free base); 1195768-06-9 | C23 H20 F3 N5 O2 S2 . C H4 O3 S | 615.668 |
 | trametinib dimethyl sulfoxide (USAN) | 1187431-43-1 | C26 H23 F I N5 O4 . C2 H6 O S | 693.528 |
| bevacizumab (Rec INN) | 216974-75-3 |
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