OU College of Medicine Researcher Earns Grant to Study ‘Chemo Brain’

Anna Csiszar, M.D., Ph.D.

Up to 75% of cancer survivors treated with chemotherapy are affected by “chemo brain,” with symptoms such as difficulty focusing, processing information, learning new tasks, and planning or making decisions. Thus far, scientists have not been able to pinpoint the exact cause, but a researcher at the OU College of Medicine has been awarded a $1.6 million federal grant to study a promising new hypothesis.

Chemo brain is an underrecognized but potentially debilitating side effect of cancer treatment. The phenomenon, formally known as chemotherapy-related cognitive impairment, can arise while patients are undergoing treatment, and it can persist months to years later. Because cognitive symptoms range from mild to severe, and can be hard to identify because of other factors like fatigue or depression, doctors may not recognize the early signs, and there are no strategies to prevent or reverse the problem once it begins.

“It’s very frustrating for cancer survivors to experience these long-term side effects,” said Anna Csiszar, M.D., Ph.D., a researcher in the Center for Geroscience and Healthy Brain Aging and a professor in the Department of Biochemistry and Molecular Biology. “It often causes problems in the workforce when people are unable to focus on their work. And because the survival rate for cancer is increasing, more and more

patients are suffering from chemo brain. Furthermore, older adults are at the highest risk of developing cancer, and they may already be experiencing some of the cognitive challenges associated with aging, such as dementia. Adding another deficit can significantly impact the functioning and independence of older patients, leading to faster decline even after they have survived cancer.”

Csiszar, who received the grant from the National Cancer Institute, focuses on aging and age-related cognitive impairment in her research lab. As it turns out, chemo brain has some similarities. In reviewing the scientific literature, Csiszar realized that the human brain after chemotherapy looks similar to the accelerated brain aging research models that she uses in her other projects. She began forming some ideas and, in collaboration with several OU colleagues in cancer treatment and research, began studying chemo brain.

Csiszar knew that because of the blood-brain barrier, chemotherapy agents are not able to enter the brain tissue and directly cause damage. Nor are the neurons damaged because they are resistant to chemotherapy agents. Her hypothesis is that chemotherapy is damaging the endothelial cells of the brain vasculature, the network of blood vessels that is key to healthy brain functioning. Endothelial cells are on the lookout for drugs and changes in circulation, and they respond with regulation of blood flow, barrier capacity and inflammation. When endothelial cells are damaged — because of chemotherapy, for example — they undergo cellular senescence, which puts them in a suspended state. Researchers call them “zombie cells.”

“Senescent cells are unable to fulfill their normal function, but they are also unable to die,” Csiszar said. “That’s why they are called ‘zombie cells.’”

Csiszar believes that “zombie cells” impair the flow of blood to the brain and set off a cascade of changes that eventually lead to cognitive impairment. She also aims to prove through her research that eliminating the “zombie cells” will prevent or reverse cognitive impairment. Pharmaceutical companies are already developing drugs, for other indications, that will selectively eliminate “zombie cells,” she said.

Csiszar’s project is part of a growing gero-oncology research group at OU. She oversees a large tissue bank for the Oklahoma Center for Geroscience and Healthy Brain Aging, which other researchers use for projects that span both aging and cancer. Her funding from the National Cancer Institute to study chemo brain underscores the value of collaborations between clinicians and basic science researchers to improve the lives of Oklahomans, she said.

“There is truly an intersection between geroscience and cancer biology, prevention and treatment,” she said. “These teams represent the future of research, and we have wonderful momentum on our campus.”

Research reported in this story is supported by the National Cancer Institute, a component of the National Institute of Health, under the award number 1R01CA255840-01. Local funding organization Presbyterian Health Foundation also provided support.