Of the 14 million cancer survivors in the United States, a significant number experience a serious side effect called chemotherapy-induced cognitive impairment (CICI). While easily recognized, little is known about the etiology of this condition, also known informally as “chemo brain.” CICI can significantly reduce patients’ quality of life with serious, even devastating, symptoms such as memory lapses, difficulty concentrating, negative impacts on multitasking, confusion and fatigue.

Three University of Kentucky Markey Cancer Center researchers are tackling this problem head-on, serving as principal investigators on a new $2.3 million grant awarded by the National Institutes of Health:

• Allan Butterfield, professor in the UK College of Arts and Sciences' Department of Chemistry, is renowned for his work in neurochemistry and Alzheimer’s research. Previously he has demonstrated that mitochondrial injury, mediated by reactive oxygen species, is an important mechanism of CICI.
• Daret St. Clair, professor in the UK College of Medicine's Department of Toxicology and Cancer Biology, is a leading collaborator with Butterfield on CICI research. The primary research focus of her laboratory is in the area of the mitochondrial antioxidant defense system and its response to oxidative stress, which may induce CICI.
• Subbarao Bondada, professor in the UK College of Medicine's Department of Microbiology, Immunology and Molecular Genetics, focuses primarily on B cell biology, blood cancers and myelodysplastic syndromes. His expertise in B cell biology has led the team into the investigation of the contribution of immune responses to CICI.

The new award, titled "A redox-mediated mechanism of chemotherapy-induced cognitive impairment,” theorizes a novel mechanism of CICI and identifies strategies for its prevention. The research is designed to gain an understanding of damage mechanisms and to identify the cells that produce agents during chemotherapy that lead to cognitive impairment.

The team of three researchers will test the proof-of-concept in an experimental cancer therapy setting using two prototype chemotherapy agents. They have been collaborating with clinical investigators in the Markey Cancer Center, including Dr. Rachel Miller, an associate professor in UK Gynecologic Oncology Services. If successful, the project will generate new insights required to develop effective clinical approaches specifically designed to prevent CICI without reducing chemotherapeutic efficacy, and will significantly improve the quality of life for millions of cancer survivors.