Scientists Find Genes That Make Brain Tumours Resistant to Treatment

18 November 2010 – ICR scientists have pinpointed two genes that can predict whether patients with an aggressive type of brain tumour will respond to the gold standard treatment.

Glioblastoma patients have a poor prognosis; however, the chemotherapy drug Temozolomide can give a modest improvement in survival to some – but not all – patients.
The drug, which is taken orally, works by crossing the blood-brain barrier and damaging tumour cells’ DNA, triggering their death. Researchers have previously found a gene linked to Temozolomide resistance called MGMT, which allows the tumour to repair the DNA damage the drug causes, but it could not explain all patients’ failure to respond.
The latest study, led by Dr Chris Jones and published in Cancer Research, examined glioblastoma samples that were drug resistant without high levels of MGMT and found high levels of proteins from two other genes - called HOX9A and HOX10A.

Both HOXA9 and HOXA10 were associated with drug resistance and shorter survival in children with glioblastoma. The research team further showed that the genes are overexpressed in response to a pathway called PI3 kinase. Treating cells with a drug that inhibited this pathway reduced the amount of HOXA9 and HOXA10 protein present and overcame resistance to Temozolomide. This raises the possibility that resistance to this drug could be overcome; however, further testing would be required to confirm this.

The findings may help to identify patients unlikely to benefit from the drug, so they are not put at risk of potentially serious side-effects, including a drop in white blood cells that can lead to increased infection risk and fertility loss.