Cancer neuroscience and glioma: clinical implications

Abstract

In recent years, it has been increasingly recognized that tumor growth relies not only on support from the surrounding microenvironment but also on the tumors capacity to adapt to - and actively manipulate - its niche. While targeting angiogenesis and modulating the local immune environment have been explored as therapeutic approaches, these strategies have yet to yield effective treatments for brain tumors and remain under refinement. More recently, the nervous system itself has been explored as a critical environmental support for cancer, with extensive neuro-tumoral interactions observed both intracranially and in extracranial sites containing neural components. In the brain, interactions between glioma cells as well as metastatic lesions with neural components have clinical implications for diagnostics, risk assessments, neurological sequelae, and the development of innovative therapeutics. Here, we review these neuro-tumoral dynamics, emphasizing aspects relevant to neurosurgical practice.

Keywords: Extracellular vesicles; Glioblastoma; Immunosuppression; Methylation profiles; Neural signature; Neuroglial communication.

Fig. 1

Conceptual description of the path to the synchronicity of multiple genomic /epigenetic signatures resulting in diverse cellular programs within GBM. Hierarchically, after the initial oncogenic event resulting in the initial signature level (SL 1), mostly genetics based, the further evolving gene-expression / epigenetic signatures will be modified by local selective pressure such as hypoxia or external pressures like radiation and chemotherapy (SL 2). In the definitive, multilayered glioblastoma with increasing radial distance from the necrotic core, infiltration into the brain and fending off the immune surveillance result in increasingly complex adaptive signatures also by acquisition of neural characteristics (neural adaptive mimicry, NAM) with increasing tumor vitality and subsequent poor patient survival. (Adopted in principle from Greenwald et al. [23], referring to gene expression signatures.)