Chemobrain in blood cancers: How chemotherapeutics interfere with the brain's structure and functionality, immune system, and metabolic functions

• Published in: Medicinal research reviews Vol. 44; no. 1; pp. 5 - 22
• Main Authors: Skurlova, M., Holubova, K., Kleteckova, L., Kozak, T., Kubova, H., Horacek, J., Vales, K.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-01-2024
• Subjects: Animals; BBB; Blood cancer; Blood-brain barrier; Brain - metabolism; chemobrain; Chemotherapy; Chemotherapy-Related Cognitive Impairment - metabolism; Chemotherapy-Related Cognitive Impairment - pathology; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - pathology; Humans; Immune System; Inflammation; Metabolism; Morphology; Neoplasms - drug therapy; Neurodegeneration; neuroinflammation; chemobrain; BBB; neuroinflammation; chemotherapy; blood cancer
• ISSN: 0198-6325; 1098-1128; 1098-1128
• DOI: 10.1002/med.21977

Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well‐being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy‐induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood–brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo‐drug's effects on cognition in cancer are not direct and/or in‐direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy‐induced cognitive impairment.
Highlights
An inflammatory burst could be the background for chemobrain in blood cancer. In acute phases, blood sera of patients contain massive levels of proinflammatory cytokines.
In blood cancer, direct cytokine neurotoxicity, and neuroinflammation occur in concert with cytokine‐mediated disruption of the blood–brain barrier.
A blood cancer drug exerts multifaceted effects on chemobrain:
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Methotrexate combines brain structure damage with persisting chemotherapy‐induced neuroinflammation.
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Doxorubicin fulfills the concept of chemotherapy‐induced neuroinflammation with peripheral origin.