April 21, 2008 -- Scientists have discovered that a popular chemotherapy
drug affects healthy brain cells long after treatment ends. It's a finding that
provides further validation to the millions of Americans who develop long-term
cognitive problems after receiving the cancer-killing medication.
Many cancer survivors report short-term memory loss and difficulty
concentrating during and shortly after treatment, but for some the problems
Until recently, doctors told cancer patients who developed memory loss,
seizures, vision problems, and dementia that their ailments -- collectively dubbed
"chemo brain" -- resulted from treatment-related fatigue, depression, and anxiety.
While more and more scientists agree that chemotherapy drugs may negatively
affect brain function in certain cancer patients, how this occurs is largely
unknown. Now, researchers at the University of Rochester and Harvard Medical
School have provided what could be the first evidence of a biological cause of
the lingering effects of chemo brain.
Reporting in the April 22 issue of Journal of Biology, researcher
Mark Noble, PhD, director of the University of Rochester Stem Cell and
Regenerative Medicine Institute, links the drug 5-fluorouracil (5-FU) to
extensive damage among specific groups of cells in the central nervous system;
5-FU is a widely used chemotherapy drug that has been a part of America's
cancer-killing arsenal for more than 40 years. It is prescribed for those with
a variety of cancers, including breast, stomach, colon, and pancreatic cancer.
For the study, Noble and colleagues performed tests on mice and in test
tubes with varying doses of the cancer drug. The doses were comparable to those
given to cancer patients.
After months of exposure, the drug caused considerable damage to central
nervous system cells called oligodendrocytes and the dividing stem cells from
which they developed.
The findings suggest that the drug directly targets oligodendrocytes.
Oligodendrocytes produce myelin, the fatty substance that helps insulate and
protect nerve-conducting fibers. Without adequate myelin, normal nerve
signaling is disrupted.
"Our studies demonstrate that systemic treatment with 5-FU is associated
with both acute and delayed toxicity reactions, outcomes that are of particular
concern because of the use of this agent in the treatment of many cancers,"
The team's findings parallel observations of earlier studies involving
cancer survivors with cognitive difficulties in which brain scans revealed a
loss of myelination.
"It is clear that, in some patients, chemotherapy appears to trigger a
degenerative condition in the central nervous system," Noble says in a news
release. "Because these treatments will clearly remain the standard
of care for many years to come, it is critical that we understand their precise
impact on the central nervous system, and then use this knowledge as the basis
for discovering means of preventing such side effects."