Researchers have not only confirmed that tamoxifen induces cognitive dysfunction in users, they have also found an existing treatment that can prevent this adverse effect.
Widely used to combat breast cancer, tamoxifen is regarded as a benign antihormonal agent. However, clinical studies indicate that exposure to this drug is associated with adverse neurologic consequences, wrote Mark Noble, PhD, director of the University of Rochester Stem Cell and Regenerative Medicine Institute in Rochester, New York, and fellow investigators in The Journal of Neuroscience (2013;33:15069-15074).
Noble and team uncovered a scientific basis for what many women report anecdotally regarding tamoxifen’s toxicity to brain cells: Their laboratory and mouse studies revealed that the drug is toxic for a variety of central nervous system (CNS) cell populations and that it increases cell death and reduces cell division in areas of the brain.
Following this discovery, Noble and colleagues screened 1,040 compounds already in clinical use or in clinical trials, eventually identifying 27 that protected essential CNS cells known as 0-2A/OPCs from tamoxifen toxicity. Further testing singled out the investigational MEK inhibitor AZD6244 as a potential therapy against the effects of tamoxifen. As noted in a statement from the University of Rochester Medical Center, AZD6244, which is also known as selumetinib, is being evaluated in several national clinical trials as a treatment for various cancers, including breast cancer.
Noble’s group showed that AZD6244 prevented tamoxifen-induced destruction of brain cells in mice while enhancing tamoxifen’s effects on breast cancer cells. In future work, the researchers plan to identify the dosage of AZD6244 that provides maximum protection and minimum disruption to differentiating brain cells. ONA