Using imaging technology that reveals whether brain tumors have a particular genetic mutation known as IDH, a team of academic and pharmaceutical company researchers has developed a way to help doctors select the right treatment, and developers to make new drugs that target the mutation.
The researchers, from MIT, Harvard University, Massachusetts General Hospital (MGH) and Agios Pharmaceuticals, write about their findings in the 11 January online issue of Science Translational Medicine.
Some of the deadliest cancers are those that affect the brain. They are known as gliomas and the chances of surviving them are virtually zero, partly due to a lack of effective treatments.
Another problem is identifying the type of glioma: patients with high-grade gliomas, known as glioblastomas, have a very poor prognosis. Patients with low-grade gliomas can survive for years, although eventually the tumors do prove fatal.
One way to identify the type of brain tumor is to look for a mutation in a gene that codes for an enzyme called isocitrate dehydrogenase (IDH). Something like 86% of low-grade gliomas contain IDH mutations.
IDH plays a part in helping cells break down sugar molecules and extract their energy for cell metabolism.
But where IDH is mutated, tumor cells start making vast quantities of a compound called 2-hydroxyglutarate (2-HG).
Previous studies have shown that 2-HG interferes with normal regulation of DNA expression, with the result that the cells revert to an immature state that promotes uncontrolled growth.
A number of drug developers are currently developing treatments that target IDH as a way to stop tumors growing.
Study co-author Matthew G. Vander Heiden, a member of the David H. Koch Institute for Integrative Cancer Research at MIT, said in a statement that some of these new treatments could be undergoing clinical trials within the next 12 months.
Vander Heiden is also the Howard S. and Linda B. Stern Career Development Professor of Biology at MIT.
In their study report, he and his colleagues describe how they used magnetic resonance spectroscopy (MRS) to analyze the magnetic properties of the atomic nuclei of the 2-HG molecule and thereby locate it in the brain.
This had been tried before, without much success, because 2-HG is not easy to distinguish from other common metabolic compounds such as glutamate and glutamine.
Lead author Ovidiu Andronesi, along with co-author Greg Sorensen, both from MGH, found a way around this: by doing the MR scans in two dimensions they could obtain enough information to distinguish 2-HG from other similar molecules.
The method doesn’t require any specialized equipment: the researchers said you can use the MRI scanners already found in most hospitals.
The only way to test for 2-HG at the moment is to do a brain biopsy and then test the sample with a mass spectrometer. While you might be able to do this at initial diagnosis, you can’t keep doing this on a regular basis, says Hai Yan, an assistant professor of pathology at Duke University who was not involved in the study.
Vander Heiden said the most exciting part of this new development is that as the drugs for treating gliomas come on stream, using MRS you will be able to tell which patients with brain tumors should be directed toward the clinical trials, and then also use it to monitor the treatment and see whether the drug they’re given is actually doing what it’s supposed to.
Written by Catharine Paddock PhD