In “Dynamin-1 is a potential mediator in cancer-related cognitive impairment,” published in Neurotherapeutics, University of California, Irvine School of Pharmacy & Pharmaceutical Sciences and School of Medicine researchers conducted human and animal studies to explore how the protein dynamin-1 (DNM1) may be involved in the development of cancer-related cognitive impairment (CRCI).
Chan Lab principal investigator and researchers Dr. Alexandre Chan, Ding Quan (Quinton) Ng, and Yong Qin Koh collaborated with Acharya Lab principal investigator and researchers Dr. Munjal Acharya, Sukesh Kumar Gupta, Casey Hudson, and Tracy Nguyen to complete the study.
“In our human study, we recruited 30 newly diagnosed adolescent and young adult participants (who have not started treatment) and 86 participants who do not have cancer. Each person completed a cognitive instrument and provided blood samples to analyze DNM1 levels within plasma extracellular vesicles,” Ng explained.
The results of the human study revealed that, before starting treatment, cancer patients had 32% lower DNM1 levels as compared to those without cancer, and after undergoing neurotoxic treatment, cancer patients with cognitive impairment showed a 46% decrease in DNM1 levels compared to those without impairment.
“These differences were not explained by cognitive impairment among young adult healthy participants,” said Ng. “These findings suggest that both cancer itself and cognitive issues caused by neurotoxic cancer treatment are linked to lower DNM1 levels, pointing to DNM1 as a potential mediator in CRCI.”
Following the human study, researchers from the Acharya Lab led an animal study using mice (human studies into if DNM1 levels in the blood reflect changes in the brain can only be completed through autopsy).
The team observed that DNM1 levels in the hippocampus of female mice with breast cancer treated with chemotherapy dropped by over 40%, as well as declines in memory performance. The changes were not seen in healthy mice or those that had not undergone chemotherapy.
“Together, our human and animal studies consistently show that reduced DNM1 is linked to CRCI,” Ng stated. “This makes DNM1 a promising biomarker and potential therapeutic target for managing CRCI.”
These findings could lead to further research into the factors that may impact DNM1 levels and CRCI, such as age, income, and types of cancer treatments, which could assist in identifying who could most benefit from treatments aimed at augmenting DNM1. The team has recently received a UCI Susan & Henry Samueli College of Health Sciences (COHS) Pilot Studies award to study the potential of augmenting DNM1 levels to mitigate CRCI.
The study is part of a greater effort to understand and alleviate CRCI, a side effect of cancer and cancer treatment that affects up to 75% of patients.
“CRCI is particularly concerning for adolescent and young adult cancer patients, as it increases the risk of unemployment, difficulties in completing college, and needing support for independent living. However, there remains a lack of quality evidence for effective ways to prevent or treat CRCI despite the consequences, making it a critical unmet need in cancer care,” said Ng.
