Abstract
People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood-brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis.
Highlights
This study suggests that peripheral tumour growth alone can cause neurological dysfunctions through IL6-mediated inflammatory signalling, a reduction of hippocampal neurogenesis and decreased levels of hippocampal brain-derived neurotrophic factor (BDNF) and COX-2 (Yang et al, 2014)
The authors further showed that Ventral tegmental area (VTA) activation altered the levels of noradrenaline in the bone marrow. This reduced the number of myeloid-derived suppressor cells (MDSCs), which normally promote tumour growth via stimulation of angiogenesis and inhibition of anti-tumour immunity. These findings indicate that central VTA stimulation, and enhanced levels of reward and motivation in mice, can modulate the immune system via sympathetic nervous system (SNS)-mediated suppression of MDSCs (Ben-Shaanan et al, 2018)
Whereas the neurological implications of ant-ineoplastic therapies have received a substantial amount of interest, the existence of cognitive and affective disorders, before treatment has started, indicates that the full aetiology of these complications cannot be solely explained by the anti-cancer treatment itself
Summary
Tumour brain: Pretreatment cognitive and affective disorders caused by peripheral cancers. People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. The reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis. KEYWORDS blood–brain barrier, cancer-related cognitive impairment, circadian rhythms, depression, hypothalamic–pituitary–adrenal axis, inflammation, stress, tumour brain
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