Molecular insights into the effects of cancer and chemotherapy on the brain

Abstract

An array of central nervous system complications, neurological deficits, and cognitive impairments come about and persist as a result of cancer and cancer treatments. These conditions are known as ‘tumor brain’ and ‘chemo brain’, respectively, and affect many cancer survivors. We proposed that the mechanisms behind tumor and chemo brain were epigenetic and associated with aberrant global gene expression and metabolome deregulation. We used mouse TumorGraft models of breast, lung, and pancreatic cancer, and sarcoma to profile the epigenetic, transcriptome, small RNAome, and metabolome changes in chemo-treated tumor-bearing mice, as compared to untreated tumor-bearing mice, and to control mice. We noted that tumor presence alone caused oxidative stress and affected global gene and small RNA expression, DNA methylation, and metabolic activity in the brain. Chemotherapy affected similar domains, at times seeming to build on tumor effects. The observed molecular changes strongly resembled those associated with neurodegenerative diseases and brain aging.