Researchers have developed a novel animal model showing that four commonly used chemotherapy drugs disrupt the birth of new brain cells, and that the condition could be partially reversed with the growth factor IGF-1.
Published early online in the journal Cancer Investigation, the University of Rochester Medical Center study is relevant to the legions of cancer survivors who experience a frustrating decline in cognitive function after chemotherapy treatment, known as chemo-brain.
"It is not yet clear how our results can be generally applied to humans but we have taken a very significant step toward reproducing a debilitating condition and finding ways to treat it," said Robert Gross, M.D., Ph.D., professor of Neurology and of Pharmacology and Physiology at URMC and principal investigator of the study.
Chemo-brain is a newly recognized condition. The URMC team found surprising data about how the four drugs impact the brain, Gross said, and they are the first to report that the experimental insulin-like growth factor, IGF-1, may be beneficial.
The study was funded by a Department of Defense grant to Gross and by the National Cancer Institute to co-investigator and lead author, Michelle Janelsins, Ph.D., research assistant professor of Radiation Oncology at the James P. Wilmot Cancer Center.
More than 11 million Americans are living today after receiving a cancer diagnosis. Many of them have endured chemotherapy and although the side effects during treatment are well known, the lingering neurological effects are more puzzling. Patients often report memory lapses, trouble concentrating, confusion, difficulty multi-tasking and slow thinking for weeks, months or years after treatment ends.
The URMC team hypothesized that cognitive problems might stem from chemo destroying the ability of brain cells to regenerate in the hippocampus, which is primarily involved in memory formation and mood. They sought a way to find the mechanisms at work and to manage the adverse effects on the brain before, during and after chemotherapy treatment.
Researchers also hypothesized that chemotherapy drugs known to cross the blood-brain barrier would be a bigger threat to brain cells than drugs that do not cross the blood-brain barrier. To test the hypothesis, they investigated the effects of routinely used doses of cyclophosphamide and fluorouracil, which do cross into the brain, against paclitaxel and doxorubicin, which do not.
Unexpectedly, all four drugs caused a significant breakdown in brain cell proliferation in the animal model. A statistical analysis of cell regeneration showed a 15.4 percent reduction in new brain cells following fluorouracil, a 30.5 percent reduction following cyclophosphamide, a 22.4 percent reduction following doxorubicin, and a 36 percent reduction following paclitaxel.