by ecancer reporter Emma Campell 

Scientists from the University of Pittsburgh Cancer Institute have opened a door that could lead to more effective treatment for people with glioblastoma multiforme, one of the most common types of brain tumour in adults.

According to the National Cancer Institute, glioblastoma multiforme accounts for about 15 percent of all brain tumours, and patients with the disease usually survive less than 15 months after diagnosis.

As explained by the study’s lead author David Svilar, a student in the Medical Scientist Training Program at the University of Pittsburgh School of Medicine, “The current standard of care for people with this type of cancer is to remove as much of the tumour as possible, and then treat with radiation and temozolomide. However, glioblastoma multiforme is highly resistant to this chemotherapy drug, so we need to find better treatments to improve the patient survival rate.”

In this latest research, published in Molecular Cancer Research, the researchers found that over 125 genetic components were needed for the cells’ resistance to temozolomide. This exciting discovery could open doors for the development of new ways to overcome the problem of drug resistance in treating brain tumours.

Using a cell line that had been derived from a temozolomide-resistant brain tumour, the scientists blocked the activity of over 5,000 genes in the cells to find out if any of them were needed for drug resistance. The detailed study revealed over 125 genetic components that, when impaired, enabled temozolomide to kill the tumour cells. Included in these, were genes that until now had not been linked to this drug resistance.

Scientists can now build on this research to look for ways to block these genes and develop new drugs to increase the sensitivity of cancer cells to chemotherapy.

“Our hope is that drug companies will use our findings to develop adjuvant chemotherapy drugs that will vastly improve patient survival from this deadly cancer,” said senior author Robert Sobol, a scientist at UPCI and an associate professor in the departments of Pharmacology & Chemical Biology and Human Genetics.

Although some clinical trials are already underway to test ways of stopping or slowing down the development of drug resistance in brain tumours, so far, none of them has proved effective. This new research could provide the foundation needed to improve treatment and extend life expectancy for people with glioblastoma multiforme.

Reference
D Svilar, M Dyavaiah, AR Brown, et al. Alkylation sensitivity screens reveal a conserved cross-species functionome. Molecular Cancer Research. doi: 10.1158/1541-7786.MCR-12-0168