Brain-Cancer Interactions in Cancer Hosts

This Research Topic focuses on cancers originating outside the central nervous system across the lifespan (including paediatric, adolescent, and adult populations) and their mechanistic and clinical interactions with the brain, including systemic effects and secondary central nervous system involvement.Emerging evidence demonstrates that cancers outside the central nervous system profoundly influence the cancer host’s brain, producing cognitive, affective, and neural alterations even in the absence of direct metastasis. Cancer-related cognitive impairment (CRCI) affects up to one-third of patients and survivors, with measurable deficits in memory, executive function, and processing speed. Neuroimaging studies reveal structural and functional changes (including gray matter loss, disrupted white matter integrity, and altered connectivity) across multiple cancer types. This includes both indirect systemic effects and direct central nervous system involvement, such as brain metastases and leptomeningeal disease, primarily in the context of solid tumours.Mechanistically, systemic inflammation and tumor-derived cytokines (e.g., IL-6, TNF-α, IL-1 family) can cross or signal through the blood-brain barrier, activating microglia and astrocytes, and disrupting myelination, synaptic pruning and neuronal homeostasis. Beyond indirect effects, tumors engage directly with neural systems: peripheral malignancies are regulated by sympathetic, parasympathetic, and central circuits that shape tumor growth and immune surveillance, while emerging evidence suggests that tumour–neural interactions may also involve direct and indirect signalling pathways influencing brain function and systemic disease progression. Together, these findings position the brain as both a vulnerable target and an active regulator of systemic cancer biology.Understanding how cancer affects the brain requires disentangling complex, overlapping factors. A major challenge is distinguishing causality from correlation. Specifically, to what extent do tumor-derived signals, psychological stress, or treatment contribute to observed neural changes? This task is complicated by the heterogeneity among cancers: different tumor types, stages, and anatomical locations may exert distinct effects, with some provoking stronger systemic inflammation than others. Brain changes may emerge at various stages, including during early tumor growth, or later during or after treatment. Yet, the temporal trajectories of recovery versus deterioration remain unclear.Mechanistically, while numerous pathways have been proposed (e.g., cytokine signalling, neuroimmune activation, metabolic disruption), detailed molecular and cellular mechanisms are not fully elucidated. Recent research is beginning to explore the roles of tumor-infiltrating nerves and long-range neural circuits that may link peripheral tumors to brain function. Individual susceptibility also plays a critical role; factors such as genetics, age, comorbidities, and cognitive reserve likely influence vulnerability but remain understudied.In addition, emerging areas such as treatment-related neurocognitive effects (e.g., hematopoietic stem cell transplantation and systemic therapies) across the lifespan are of growing interest, particularly where brain–immune system signalling mechanisms remain only partially understood.Despite growing awareness, therapeutic strategies directly targeting cancer–brain interactions are limited, and interventions like exercise or cognitive training, while promising, lack robust evidence specific to cancer-related neural effects. Studying cancer–brain interactions is therefore essential not only for alleviating the neurocognitive and psychiatric burden of cancer, but also for identifying novel biomarkers and therapeutic strategies that leverage neuroimmune and neurocircuit mechanisms to improve therapy design and outcomes, quality of life and morbidity-free survivorship.This Frontiers in Oncology Research Topic seeks to compile work under the following specific scopes:(1) Clinical scope & cancer-related cognitive impairment (CRCI)(2) Neuroimaging evidence (structure, function, metabolism)(3) Peripheral inflammation/cytokine signalling (mechanistic link),(4) Neuroimmune cells and brain metastasis biology,(5) Nervous system-tumor interactions (tumor innervation, neural control of immunity).Studies should primarily focus on solid tumours originating outside the CNS; inclusion of haematologic malignancies should be limited to cases where clear mechanistic insights into cancer–brain interactions are provided.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases, which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Tatiana Wolfe, Renata Leoni, Joy Perrier, Qi Ye Source: https://www.frontiersin.org/research-topics/78837/brain-cancer-interactions-in-cancer-hosts