Cognitive impairments and cancer chemotherapy: translational research at a crossroads

Cancer chemotherapy is often associated with cognitive deficits which may remain after the treatment has ended. As more people survive cancer, concern is increasing about the impact of these problems with memory and executive function when they return to everyday life. When chemotherapeutic drugs are administered to healthy animals in dosing regimens modeling those used in humans, cognitive deficits also occur, and these preclinical studies can provide information about the biological mechanisms by which the cancer fighting drugs affect the brain. Evidence from animal studies points to damage to hippocampus, particularly a disruption of neurogenesis, whereas human studies emphasize cognitive deficits associated with impairments in frontal cortical function. This discrepancy may be due more to the tasks selected by researchers, and the choice of biochemical endpoints than inherently different effects of chemotherapy in humans and rodents. These differences in approach must be reconciled if common underlying mechanisms are to be identified, with the hope of leading to novel drug or non-pharmacological treatments. This may be achieved by broadening the scope of human and animal studies, and by looking outside the topic of chemotherapy-induced cancer deficits to learn from the advances being made by studying the effects of stress and somatic disease on brain function, and the cognitive impairments now recognized to result from a wide range of mental and physical illnesses.