Drosophila melanogaster as a Model System for Human Glioblastoma

Glioblastoma (GB) is the most common and aggressive malignant primary brain tumor of the central nervous system in humans. It originates from neoplastic glial cells that infiltrate the brain parenchyma, leading to neurological symptoms, including progressive memory loss, speech and language deficits, epileptic seizures, and vomiting as hallmarks of neurodegenerative processes. Conventional therapies have failed to effectively treat GB due to its diffuse nature and high recurrence rates after treatment. To address these challenges, different models have been developed to study the early stages of gliomagenesis and cell-to-cell interactions. These include animal models, cellular lines, coculture assays, organoid models, and bioinformatics approaches. Among those models, nonmammalian models such as Drosophila melanogaster recapitulate the genetic, cellular, and physiological characteristics of GB in patients, reproducing glial proliferation, invasion, and the alteration of signaling pathways involved in tumor growth.As observed in humans, Drosophila GB model reproduces the cell-to-cell communication involving glioma cell-glioma cell and neuron-glioma cell communication as a bidirectional communication system through signals from GB to neuron or neuronal activity and signals that the tumor vampirizes from the neurons. This multicellular network appears to be crucial for GB growth and invasion, presenting promising opportunities to develop novel treatments aimed at overcoming therapy resistance.