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

Krishna, Saritha; Hervey-Jumper, Shawn L

doi:10.1002/adbi.202200047

Cited by 4 publications

(3 citation statements)

References 106 publications

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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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confidence: 99%

Glioblastoma remodelling of human neural circuits decreases survival

Krishna

Choudhury

Keough

et al. 2023

Nature

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116

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Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1–4 and gliomas increasing neuronal excitability2,5–8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron–glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

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confidence: 99%

Glioblastoma remodelling of human neural circuits decreases survival

Krishna

Choudhury

Keough

et al. 2023

Nature

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116

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“…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 ).…”

Section: Novel Modeling Approaches Of Systems-level Processesmentioning

confidence: 99%

“…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.…”

Section: Novel Modeling Approaches Of Systems-level Processesmentioning

confidence: 99%

Advances in computational and translational approaches for malignant glioma

et al. 2023

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Gliomas are the most common primary brain tumors in adults and carry a dismal prognosis for patients. Current standard-of-care for gliomas is comprised of maximal safe surgical resection following by a combination of chemotherapy and radiation therapy depending on the grade and type of tumor. Despite decades of research efforts directed towards identifying effective therapies, curative treatments have been largely elusive in the majority of cases. The development and refinement of novel methodologies over recent years that integrate computational techniques with translational paradigms have begun to shed light on features of glioma, previously difficult to study. These methodologies have enabled a number of point-of-care approaches that can provide real-time, patient-specific and tumor-specific diagnostics that may guide the selection and development of therapies including decision-making surrounding surgical resection. Novel methodologies have also demonstrated utility in characterizing glioma-brain network dynamics and in turn early investigations into glioma plasticity and influence on surgical planning at a systems level. Similarly, application of such techniques in the laboratory setting have enhanced the ability to accurately model glioma disease processes and interrogate mechanisms of resistance to therapy. In this review, we highlight representative trends in the integration of computational methodologies including artificial intelligence and modeling with translational approaches in the study and treatment of malignant gliomas both at the point-of-care and outside the operative theater in silico as well as in the laboratory setting.

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An Overview of Reviews on Predictors of Neurorehabilitation in Surgical or Non-Surgical Patients with Brain Tumours

Gambarin,

Malgrati,

Di Censo

et al. 2024

Life

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(1) Background. People suffering from brain cancer, regardless of histological tumour characteristics, often experience motor disturbances, cognitive–behavioural difficulty, language impairments, and functional and social limitations. The current treatment approach entails surgery and adjuvant therapy such as chemotherapy and radiotherapy combined with intensive rehabilitation. The primary focus of rehabilitation is usually motor and functional recovery, without specifically addressing the patient’s quality of life. The present systematic review identifies and evaluates the predictors of functional and cognitive rehabilitation outcomes and their influence on quality of life in adult patients with brain cancer. (2) Methods. Three electronic databases (PubMed, Elsevier, Cochrane) were searched for reviews about functional, cognitive, and quality-of-life outcomes in patients with central nervous system tumours, including articles published between January 2018 and May 2024. (3) Results. The search retrieved 399 records, 40 of which were reviewed. Five main areas of predictive factors were identified: diagnosis, therapy, complications, outcomes (in the motor, cognitive, and quality-of-life categories), and tailored rehabilitation. (4) Conclusions. These indicators may inform integrated care pathways for patients with primary central nervous system tumours.

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

Cited by 4 publications

References 106 publications

Glioblastoma remodelling of human neural circuits decreases survival

Glioblastoma remodelling of human neural circuits decreases survival

Advances in computational and translational approaches for malignant glioma

An Overview of Reviews on Predictors of Neurorehabilitation in Surgical or Non-Surgical Patients with Brain Tumours

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