Unlocking the Cause of 'Chemo Brain'

Researchers Find Clues That Help Explain Mental Affects of Chemotherapy

From the WebMD Archives

Nov. 29, 2006 -- The drugs used in cancer treatment appear to be as harmful to healthy brain tissue as to the cancer itself, according to newly reported cellular and animal studies that might explain the poorly understood condition known as "chemo brain."

Months and even years after chemotherapy, some cancer survivors report problems with memory, learning, attention, concentration, and other aspects of mental function.

There has been much speculation that even standard doses of cancer drugs can cause long-term brain damage, but there is almost no scientific evidence to back up the claim.

"Patients have been complaining about this for decades, but, for the most part, oncology docs have not taken it seriously," University of Rochester neurobiology professor Mark Noble, PhD, tells WebMD.

In a series of experiments reported in the latest issue of the Journal of Biology, Noble and colleagues identified a potential physiological cause for chemo brain.

"[Ours] is the first study that puts chemo brain on a sound scientific footing, in terms of neurobiology and cellular biology," Noble says.

Brain and Cancer Cells

In one experiment, the researchers exposed several different populations of healthy brain cells to clinically relevant levels of three commonly used chemotherapy drugs -- carmustine, cisplatin, and cytarabine. They also exposed several human cancer cell lines to the drugs.

They found that the drugs were more toxic to healthy brain cells than to cancer cells. Exposure levels that typically killed 40% to 80% of the cancer cells also killed 70% to 100% of the brain cells.

Studies in mice revealed that healthy brain cells continued to die for at least six weeks after treatment.

The researchers speculated on two possible ways that the destruction of healthy brain cells may affect mental function.

Even at low exposure levels, the drugs killed cells that are essential to learning and memory.

And the drugs also killed cells that are essential to nerve signaling within the central nervous system. When this transmission is disrupted, neurological problems commonly occur.

Many Unanswered Questions

The impact of these cellular changes on the human brain is not well understood. It is clear that some cancer survivors have more cognitive problems than others and many experience no problems at all.


In a study from Amsterdam, mental impairment was identified in roughly 30% of breast cancer patients treated with chemotherapy.

"We have no way of knowing which patients will have problems and which ones won’t," he says.

The University of Rochester researchers also hope to learn ways to minimize the cognitive impact of chemotherapy without reducing its effectiveness.

In an accompanying editorial, University of Buffalo professor of neurology and pediatrics Patricia K. Duffner, MD, wrote that a better understanding of the long-term impact of cancer treatment on brain function is critical.

She called the University of Rochester research a "wake-up call for neuro-oncologists."

In the early 1980s, Duffner conducted some of the first studies on the effects of radiation on the brains of children with brain tumors.

The realization that radiation causes brain damage in children changed clinical practice. Today, fewer children with cancer are treated with radiation or they are treated with lower doses than were once considered routine.

"It is clear [from the latest research] that chemotherapy is potentially as neurotoxic as radiation, and much closer attention needs to be paid to the long term follow-up of both children and adults who receive this form of therapy," she writes.

WebMD Health News Reviewed by Louise Chang, MD on November 29, 2006


SOURCES: Dietrich, J. Journal of Biology, Nov. 30, 2006; vol 5: online edition. Mark Nobel, PhD, professor of genetics, neurobiology and anatomy, University of Rochester, N.Y. Patricia K. Duffner, MD, professor of neurology and pediatrics, University of Buffalo School of Medicine, N.Y. Schagen, S. Cancer, Feb. 1, 1999; vol 85: pp 640-650.

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