Malaria Drug May Inhibit Some Early Cancers

[Guest guest]

[Drug might find some use in some lymphomas. The downside is it

appears to only work on 'early' cancers, including Burkitt's Lymphoma,

and requires a functional p53 gene.]

Science News

Week of Jan. 5, 2008; Vol. 173, No. 1 , p. 3

New Task: Malaria drug might inhibit some cancers

Seppa

In the 1970s and 1980s, researchers in Tanzania distributed millions

of doses of chloroquine to children as part of a 5-year

malaria-prevention project. While the study yielded only mixed results

against that disease, the researchers noticed a striking drop in cases

of Burkitt's lymphoma, a blood cancer.

New studies in mice show that chloroquine may indeed prevent Burkitt's

lymphoma and also a rare disease called ataxia telangiectasia that can

lead to leukemia.

Burkitt's lymphoma is a cancer of B lymphocytes. A hyperactive version

of a gene called myc turns these white blood cells malignant. The

downward spiral typically begins with DNA damage that is not properly

repaired. That leads to movement of DNA sections, including the myc

gene, to unfamiliar locations on a chromosome, which can result in myc

overactivation.

The protein that myc encodes, when superabundant, incites B

lymphocytes to replicate out of control, B. Kastan, a

pediatric oncologist at St. Jude Children's Research Hospital in

Memphis, Tenn., and his colleagues report in the January Journal of

Clinical Investigation.

Spurred by myc proteins, proliferating cells maintain a nutrient

supply by hijacking a natural cell-housekeeping process called

autophagy, in which cells chop up and dispose of damaged or obsolete

cell components such as proteins. Autophagy also comes in handy during

famine or other stressful times, recycling processed compounds as

nutrients to keep the cell going.

Burkitt's lymphoma cells, which have voracious appetites, commandeer

the process to accommodate their growth needs, says Kastan.

Enter chloroquine, which targets cancerous cells that make excess myc

protein and stalls autophagy in those cells. In experiments on mice

with a hyperactive myc gene—a model of Burkitt's lymphoma—animals

given chloroquine survived 265 days on average, while mice without it

lived 98 days.

A precancerous sign of Burkitt's lymphoma is a soaring white blood

cell count. Kastan and his team found that just three doses of

chloroquine normalized such counts that were starting to rise in young

mice.

However, mice allowed to develop full-blown lymphoma before receiving

chloroquine didn't benefit from the drug. The scientists found that

chloroquine works only in the presence of a functional

tumor-suppressing protein called p53. Established tumors can get the

upper hand on p53 and silence the gene that encodes it.

Taken together, the findings suggest how mass distribution of

chloroquine in Tanzania may have prevented many Burkitt's lymphoma

cases, Kastan and his team conclude.

But the p53 findings raise doubts that the drug will help against

established cases, says Glen Brubaker, a public health physician at

IMA World Health, based in New Windsor, Md. Brubaker, who coauthored

the original Tanzania study, says the new report is surprising

nevertheless. " Maybe we missed the direct effect of chloroquine. "

Since the myc gene has been implicated in at least 40 percent of

cancers, several groups are now investigating chloroquine's effect on

various malignancies.

The new findings suggest that chloroquine might prevent cancer in

people with premalignant or genetic conditions that predispose them to

cancer, says Chi V. Dang, a hematology oncologist at the s Hopkins

School of Medicine in Baltimore. Also, cancer patients who have

undergone surgery to remove a tumor often remain at risk of

recurrence, and chloroquine might benefit them, he speculates. " It's a

thing of beauty to discover new applications for old drugs, " Dang says.

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