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Scientists have discovered that a repurposed drug approved by the US Food and Drug Administration (FDA) is capable of erasing brain tumor cells in mice. This is according to a study published in the journal Oncotarget.
Researchers from the Johns Hopkins University School of Medicine used a drug called 5-azacytidine - used to treat a pre-leukemia condition called myelodysplastic syndrome - to target a mutation in a gene previously identified in human brain tumors (gliomas) called isocitrate dehydrogenase 1 (IDH1).
The IDH1 gene mutation was first discovered by a Johns Hopkins research team in 2008. The mutation exists in around 70-80% of lower-grade and progressive forms of brain cancer.
The researchers explain that IDH1 gene mutations disrupt the process of protein converting glucose into energy with certain DNA stands. The mutation "hijacks" the protein and makes a new molecule - 2-hydroxyglutarate - that is not normally found in the cell.
This molecule then causes groups of atoms called "methyl groups" to latch on to DNA strands.
The researchers say that although methylation is a normal cellular process, when too many methyl groups latch on to DNA, this can interfere with normal cell biology and contribute to cancer formation and growth.
For the study, the research team set out to determine whether a drug could erase the methyl groups, reversing the cancer process in cells with IDH1 mutations.
Tumor cells were obtained from patients with gliomas who were likely to have IDH1 mutations and then injected under the skin of mice. After a few months, these cells developed into tumors.
These types of tumors, the researchers say, usually develop into progressive or secondary glioblastoma in humans - the most severe form of brain cancer.
The researchers then injected the mice with 5-azacytidine over a period of 14 weeks.
The mice demonstrated a rapid reduction in tumor growth and what appeared to be a complete relapse. Once 5-azacytidine therapy was stopped, the tumors had not regrown after 7 weeks.
"Usually in the lab, we're happy to see a drug slow down tumor growth," says Alexandra Borodovsky, a graduate student in the Cellular and Molecular Medicine Program at the Johns Hopkins University School of Medicine and study author. "We never expect tumors to regress, but that is exactly what happened here."
However, the researchers note that they do expect the tumors to regrow in the future and are closely monitoring the mice.
The researchers say they are working quickly to design a clinical trial in order to test out this process on humans with gliomas.
They note that although the understanding of IDH1 mutations is growing, it has been challenging trying to develop effective therapies to target them.
Gregory J. Riggins, professor of neurosurgery and oncology at the Johns Hopkins University School of Medicine, says:
"This therapy has worked amazingly well in these mice. We have spoken with neurosurgeons here, and as soon as possible, we want to start discussing the parameters of a clinical trial to see if this will work in our patients as a follow-up to surgery."
However, the researchers warn that many treatments in the past have cured cancers in mice but have proved ineffective in humans.
Medical News Today recently reported on a study suggesting that dental cavities are linked to a lower risk of head and neck cancer.
Written by Honor Whiteman
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
Efficient Induction of Differentiation and Growth Inhibition in IDH1 Mutant Glioma Cells by the DNMT Inhibitor Decitabine, Sevin Turcan, Armida W. M. Fabius, Alexandra Borodovsky, Alicia Pedraza, Cameron Brennan, Jason Huse, Agnes Viale, Gregory J. Riggins, and Timothy A. Chan, published in the journal Oncotarget, 16 September 2013.
Visit our Cancer / Oncology category page for the latest news on this subject.
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