Common Biological Pathways Underlying the Psychoneurological Symptom Cluster in Cancer Patients

Background: A symptom cluster is a group of symptoms that occur together and are interrelated. The clinical implication of symptom cluster research is to use the clustering patterns of symptoms to understand the mechanisms for these symptoms and develop management strategies targeted at multiple symptoms. Objective: The purposes of this review were to summarize the evidence for a psychoneurological symptom cluster in cancer patients, to provide information regarding the underlying biological mechanisms for each of the psychoneurological symptoms within the cluster, and to propose possible common biological pathways that may underlie this cluster. Methods: A systematic review of the literature was conducted. Results: Empirical evidence exists to support a cluster of psychoneurological symptoms (ie, depressive symptoms, cognitive disturbance, fatigue, sleep disturbance, pain). At a molecular level, common biological pathways (ie, proinflammatory cytokines, hypothalamic-pituitary-adrenal axis, and monoamine neurotransmission system) may underlie the development of symptoms within this cluster. Activation of proinflammatory cytokines is proposed as a first stage of mechanistic pathway. However, other biological factors, such as lowered estrogen or hemoglobin levels, may influence psychoneurological cluster. Conclusion: Additional studies are needed to confirm the roles of cytokines as well as other biological factors in the development of the psychoneurological cluster and to determine the biomarkers to identify the subgroups of cancer patients who are at greatest risk for this cluster. Implications for Practice: This information can be used by researchers and clinicians to guide the selection of symptom management strategies that are ideally targeted to the biological mechanisms that underlie this symptom cluster.