The Role of mTOR Signaling in Tumor-Induced Alterations to Neuronal Function in Diffusely Infiltrating Glioma.

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates metabolic and environmental signals to regulate cell growth and survival. In the central nervous system, mTOR plays a pivotal role in neuronal development, plasticity, and circuit homeostasis. In diffusely infiltrating gliomas, including glioblastomas, mTOR signaling is frequently dysregulated and contributes to malignant progression, therapeutic resistance, and metabolic adaptation. Beyond tumor-intrinsic effects, recent evidence reveals that gliomas actively reprogram peritumoral neurons via mTOR-dependent mechanisms, leading to synaptic remodeling, hyperexcitability, and neurological symptoms such as seizures and cognitive dysfunction. These results position mTOR as a central mediator of both oncogenesis and neurological dysfunction in diffusely infiltrating glioma. While clinical trials of mTOR inhibitors in gliomas have so far shown limited efficacy, emerging data suggest these agents may ameliorate tumor-associated neurological dysfunction. This review synthesizes current knowledge of mTOR signaling across tumor and neuronal compartments in diffusely infiltrating glioma and highlights its potential as a therapeutic target at the intersection of cancer biology and neuroscience.