Breast cancer drug toxic to brain cells and central nervous system
Washington: Researchers have revealed that the breast cancer drug tamoxifen is toxic to cells of the brain and central nervous system, and produces mental fogginess similar to "chemo brain."
Corresponding author Mark Noble, Ph.D., professor of Biomedical Genetics and director of the UR Stem Cell and Regenerative Medicine Institute, said that it is exciting to potentially be able to prevent a toxic reaction to one of the oldest and most widely used breast cancer medications on the market.
Although tamoxifen is relatively benign compared to most cancer treatments, it nonetheless produces troubling side effects in a subset of the large number of people who take it.
By studying tamoxifen's impact on central nervous system cell populations and then screening a library of 1,040 compounds already in clinical use or clinical trials, his team identified a substance known as AZD6244, and showed that it essentially eliminated tamoxifen-induced killing of brain cells in mice.
Noble's team first identified central nervous system (CNS) cells that are most vulnerable to tamoxifen toxicity. Chief among these were oligodendrocyte-type 2 astrocyte progenitor cells (O-2A/OPCs), cells that are essential for making the insulating sheaths (called myelin) required for nerve cells to work properly.
Exposure to clinically relevant levels of tamoxifen for 48 hours killed more than 75 percent of these cells.
The study has been published in the Journal of Neuroscience.