Drug erases human brain tumours in mice

Researchers have found that a re-purposed FDA-approved drug in mice halts the growth of - and ultimately leaves no detectable trace of - brain tumour cells taken from adult human patients.
Scientists at the Johns Hopkins University School of Medicine targeted a mutation in the IDH1 gene first identified in human brain tumours called gliomas.
This mutation was found in 70 to 80 per cent of lower-grade and progressive forms of the brain cancer.
Encouraged by the new findings, the researchers say they want to work quickly to design a clinical trial to bring what they learned in mice to humans with gliomas.

"We never expect tumours to regress, but that is exactly what happened here," said Alexandra Borodovsky, who performed the experiments.
"This therapy has worked amazingly well in these mice," says study leader Gregory J Riggins.

The IDH1 gene, which stands for isocitrate dehydrogenase 1, produces an enzyme that regulates cell metabolism.
Mutations, or changes in the DNA code, force the IDH1 gene to increase production of a flawed version of the enzyme.
The flawed enzyme produces large amounts of an entirely new molecule, called 2-hydroxyglutarate. This molecule is believed to cause groups of atoms called methyl groups to latch onto the DNA strand.

Although methylation is a normal cellular process, when too many methyl groups glom onto the DNA, Riggins says, this can interfere with normal cell biology and eventually contribute to cancer formation and growth.
Borodovsky, Riggins and their colleagues thought that a drug that could strip those methyl groups might be able to reverse the cancer process in those cancers with IDH1 mutations.
They chose 5-azacytidine, which is approved to treat a pre-leukemia condition called myelodysplastic syndrome and is being tested on lung and other cancers.
Researchers obtained tumour cells from glioma patients likely to have IDH1 mutations and injected them under the skins of mice. She did this for months, before finally getting the tumour cells to grow.

Once the tumours grew, the researchers injected the mice with 5-azacytidine for 14 weeks and saw a dramatic reduction in growth and what appeared to be complete regression. Then they withdrew therapy.
Seven weeks later, the tumours had not regrown. The researchers, however, said they do expect the tumours to regrow at some point, and are still monitoring the mice.
The study was published in the journal Oncotarget.