Brain Tumor Biology

Definition

Brain tumor biology refers to the molecular, cellular, and physiological mechanisms underlying the development, progression, and behavior of primary and metastatic brain tumors. It encompasses genetic mutations, signaling pathways, tumor microenvironment interactions, and immune evasion strategies.

• Primary brain tumors – originate in the brain (e.g., glioblastoma, astrocytoma, meningioma)
• Metastatic brain tumors (BrM) – arise from cancers elsewhere (e.g., lung, breast, melanoma)

• Uncontrolled cell proliferation – due to mutations in genes like EGFR, IDH1, TP53
• Invasion of surrounding brain tissue – limits surgical resection and contributes to recurrence
• Angiogenesis – formation of abnormal blood vessels (e.g., via VEGF)
• Hypoxia and necrosis – common in aggressive tumors like glioblastoma
• Immune evasion – through upregulation of PD-L1, recruitment of regulatory cells
• Resistance to therapy – intrinsic or acquired resistance to chemotherapy, radiotherapy, and targeted agents

• Includes astrocytes, microglia, immune cells, endothelial cells, and extracellular matrix
• Influences tumor growth, invasion, and response to therapy
• Can be immunosuppressive, especially in high-grade gliomas and BrM

• Based on mutational profiles, gene expression, and epigenetics
• Example: WHO CNS tumor classification includes IDH status, 1p/19q co-deletion, MGMT methylation
• Emerging classification includes single-cell RNA-seq and spatial transcriptomics

• Understanding tumor biology helps guide diagnosis, prognosis, and treatment decisions
• Molecular profiling enables precision medicine and targeted therapy
• Insights into the biology of brain tumors inform the development of immunotherapies and novel agents

Glioblastoma exhibits a highly invasive growth pattern, driven by mesenchymal transition and hypoxic signaling, making it resistant to conventional therapies and highlighting the need for combination approaches targeting both tumor cells and the microenvironment.