A genetic flaw that’s often found in a type of brain tumour may stop the cells from fixing damage to their DNA, findings from a new US study suggest.
Researchers at Yale found that this weakness caused brain tumour cells in the lab to become highly sensitive to a drug that’s used to treat some women with ovarian cancer.
According to senior author Dr Ranjit Bindra, the discovery – if confirmed in clinical trials – could have “practice-changing implications” as it suggests a possible new approach to treating certain brain tumours.
Published in the journal Science Translational Medicine, the study looked at faults in two genes called IDH1 and IDH2. These have been found in a group of brain tumours called gliomas, alongside several other types of cancer, including melanoma.
Looking at cells in a dish, the team found that mistakes in these genes prevented the cells from being able to repair damage to their DNA.
The researchers then tested a number of different drugs on the cells, discovering that they were killed by drugs belonging to a group known as PARP inhibitors. These drugs exploit weaknesses in cells’ DNA repair machinery, and are already used to treat some cases of ovarian cancer.
The team backed up these findings by looking at glioma cells from patients in the lab and in mice, which harboured the faulty genes. They found that the tumours were particularly sensitive to a type of PARP inhibitor called olaparib (Lynparza).
Professor Anthony Chalmers, a Cancer Research UK expert on brain tumours, described the results as “hugely important” and could “revolutionise the treatment of gliomas”.
“PARP inhibitors have very few side effects and the prospect of being able to use them to treat these brain tumours is very exciting,” he added.
“The genetic faults investigated in this study are extremely common in slower-growing gliomas but are also found in up to 10% of faster-growing glioblastomas, so the number of patients who might benefit from these drugs is quite high.
“Since the treatments we have aren’t always effective for these brain tumours, it’s great to have some promising alternatives.”
The team is now designing a clinical trial to test whether drugs like olaparib could be used to treat patients whose tumours have mistakes in their IDH genes.
Sulkowski, P. L. et al. (2017). 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine.