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Restricting Use of Iron to Tumors Might be Novel Cancer Treatment

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Researchers at Mayo Clinic report in the July 2010 issue of The Journal of Clinical Investigation the first demonstration of a molecular mechanism by which a tumor oncogene can drive the use of iron, which is a critical component for cell division. The research is scheduled to appear online ahead of print June 1.

They say this work, funded by The Fraternal Order of Eagles Art Ehrmann Cancer Research Fund and the Joseph Bloom Research Fund, provides important basic biological information about how tumors form, and also suggests that restricting the use of iron to tumors might be a novel cancer treatment.

In the study, a research team led by Richard Bram, M.D., Ph.D., an associate professor of pediatrics and immunology, sought to understand why mutations in a gene called Notch1 leads to development of T-cell acute lymphoblastic lymphoma (T-ALL), a serious blood cancer diagnosed in children and young adults. They identified HIV Rev Binding Protein (Hrb) as critically important for the development of T-ALL in two different mouse models. Hrb had not previously been implicated in cancer.

The researchers found that in T-ALL cells in which Notch1 was mutated underwent apoptosis (cell death) if they lacked the Hrb gene, thus showing that Hrb provides an essential survival signal.

They discovered that Hrb accelerated the uptake of iron in the cancer cells, and this was a key mechanism behind its ability to enhance survival of the cells. Animal experiments show that mice that had reduced expression of Hrb had reduced T-ALL, and that iron-deficient mice developed Notch1-induced T-ALL significantly slower than normal.

All in all, the results identify Hrb as a novel molecular target for therapy of T-ALL, Dr. Bram says. “A new therapeutic strategy is needed because current treatments that include high-intensity chemotherapy and cranial radiation are unsatisfactory, as they frequently cause severe long-term toxicities,” he says.
“Our results strongly implicate iron metabolism in the process of oncogenesis,” he says, adding that because Hrb is not required for normal mouse development and viability, therapy directed at Hrb should theoretically have minimal toxicity.

Below is a link to an edited youtube video with Dr. Bram.


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