Neural Regulation of Cancer: Cancer‐Induced Remodeling of the Central Nervous System

Abstract

In recent years, there have been significant advances in understanding the neuronal influence on the biology of solid tumors such as prostate, pancreatic, gastric, and brain cancers. An increasing amount of experimental evidence across multiple tumor types strongly suggests the existence of bidirectional crosstalk between cancer cells and the neural microenvironment. However, unlike cancers affecting many solid organs, brain tumors, namely gliomas, can synaptically integrate into neural circuits and thus can exert a greater potential to induce dynamic remodeling of functional circuits resulting in long‐lasting behavioral changes. The first part of the review describes dynamic changes in language, sensory, and motor networks following glioma development and presents evidence focused on how different patterns of glioma‐induced cortical reorganization may predict the degree and time course of functional recovery in brain tumor patients. The second part focuses on the network and cellular‐level mechanisms underlying glioma‐induced cerebral reorganization. Finally, oncological and clinical factors influencing glioma‐induced network remodeling in glioma patients are reviewed.

Glioblastoma remodelling of human neural circuits decreases survival

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Glioblastomas remodel neural circuitsGlioblastomas and other high-grade gliomas interact with neural elements, resulting in cellular-and network-level changes [10][11][12][13] . While neurons within glioblastoma-infiltrated brain are hyperexcitable at

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Advances in computational and translational approaches for malignant glioma

“…Beyond advances in understanding the biological basis of glioma disease progression and recurrence at the molecular, cellular, and tissue level, new evidence suggests that gliomas also leverage systems-level processes ( Hadjiabadi et al, 2018 ; Stoecklein et al, 2020 ; Young et al, 2020 ; Krishna and Hervey-Jumper, 2022 ; Krishna et al, 2023 ; Winkler et al, 2023 ). In recent years, this has led to the development of entirely new fields of study including cancer neuroscience to better understand the implications of glioma-induced systems-level changes in the human brain ( Winkler et al, 2023 ).…”

“…These studies suggest that glioma cells integrate with neural elements and brain circuitry via synaptic and paracrine crosstalk as well as the development of structural changes that enable integration into the surrounding microenvironment and networks ( Venkatesh et al, 2015 ; Venkatesh et al, 2019 ; Krishna et al, 2023 ). In depth discussion of these emerging mechanisms can be found in excellent reviews by Krishna and Hervey-Jumper (2022) and Winkler et al (2023) . As these mechanisms are further elucidated, preclinical modeling of gliomas and therapy development must incorporate the study of network level changes in addition to conventional models that account for traditional hallmarks of cancer and progression.…”