Researchers from the University of Pittsburgh Cancer Institute tested more than 5,000 genes derived from glioblastoma multiforme, an aggressive brain tumour.
The genes were evaluated for their role in responding to the chemotherapy drug temozolomide.
"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," said lead author David Svilar, from the University of Pittsburgh School of Medicine.
"However, glioblastoma multiforme is highly resistant to this chemotherapy drug, so we need to find better treatments to improve the patient survival rate," Svilar said.
According to the National Cancer Institute, glioblastoma multiforme is the most common type of brain tumour in adults. It accounts for about 15 per cent of all brain tumours, and occurs in people between the ages of 45 and 70 years.
Patients with glioblastoma multiforme usually survive less than 15 months after diagnosis, and there are no effective long-term treatments for the disease.
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Temozolomide, also known by the brand name Temodar, works by modifying the cancer's DNA in a way that triggers cell death.
It has been approved by the US Food and Drug Administration for use in brain tumours and is in clinical trials for other cancers, such as melanoma and leukemia. It is well-tolerated in most patients.
"Unfortunately, some cancers - particularly glioblastoma multiforme - are able to repair the DNA damage done to the tumour by Temozolomide before the cancer cells are destroyed," said senior author Robert W Sobol, a scientist at UPCI.
"Clinical trials are underway to test drugs and chemotherapy dosing schedules to inhibit this repair, but none have proven effective to date," Sobol said in a statement.
Sobol and his colleagues identified multiple "druggable" targets that could make the cancer more sensitive to temozolomide, as well as the processes that allow the tumour to survive the onslaught of surgery, radiation and chemotherapy.
The study was published in the journal Molecular Cancer Research.