title: Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy.
abstract: One consequence of modern cancer therapy is chemotherapy related cognitive dysfunction or "chemobrain", the subjective experience of cognitive deficits at any point during or following chemotherapy. Chemobrain, a well-established clinical syndrome, has become an increasing concern because the number of long-term cancer survivors is growing dramatically. There is strong evidence that correlates changes in peripheral cytokines with the development of chemobrain in commonly used chemotherapeutic drugs for different types of cancer. However, the mechanisms by which these cytokines elicit change in the central nervous system are still unclear. In this review, we hypothesize that the administration of chemotherapy agents initiates a cascade of biological changes, with short-lived alterations in the cytokine milieu inducing persistent epigenetic alterations. These epigenetic changes lead to changes in gene expression, alterations in metabolic activity and neuronal transmission that are responsible for generating the subjective experience of cognition. This speculative but testable hypothesis should help to gain a comprehensive understanding of the mechanism underlying cognitive dysfunction in cancer patients. Such knowledge is critical to identify pharmaceutical targets with the potential to prevent and treat cancer-treatment related cognitive dysfunction and similar disorders.
authors.affiliation: School of Nursing, The University of Hong Kong, Hong Kong; Department of Anaesthesiology, The University of Hong Kong, Hong Kong. Electronic address: xmwang1@hku.hk.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: National Institute of Nursing Research, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Walitt
authors.affiliation: National Institute of Nursing Research, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Leorey
authors.initials: L
authors.lastname: Saligan
authors.affiliation: School of Nursing, The University of Hong Kong, Hong Kong.
authors.forename: Agnes F Y
authors.initials: AF
authors.lastname: Tiwari
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong.
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Cheung
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Zhang-Jin
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000139:chemically induced*; D016207:Cytokines / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011788:Quality of Life
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines
keywords: Cancer chemotherapy; Chemobrain; Cognition dysfunction; Cytokines and epigenetics