Drug targeting glioblastoma to begin clinical trial

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A drug discovery may prolong the life of people living with glioblastoma, which is the most aggressive type of brain cancer. This work, published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-3389), is leading researchers to start a human phase I/II clinical trial as early as Spring 2015.

Researchers at the University of Calgary Hotchkiss Brain Institute (HBI) and Southern Alberta Cancer Research Institute (SACRI) in Canada used tumor cells derived from 100 different glioblastoma patients to test drugs that could target the disease. When these human brain tumor-initiating cells were inserted into an animal model, researchers discovered that when combining the drug AZD8055 with temozolomide, which is a drug already taken by most patients with glioblastoma, the life of the animals was extended by 30%.

"Shutting off vital tumor growth processes can lead to the death of human brain tumor-initiating cells. Our research has identified a key process in brain tumor growth that we were able to target with AZD8055," said lead author Artee Luchman, PhD, from the University's Cumming School of Medicine and a member of the HBI.

Researchers used the new therapy to inhibit a pathway in the cancer cells known as mTOR signaling. When they put the brakes on this pathway, in combination with the current standard therapy, the result was that more of the cancer cells died. Scientists are now working with investigators at the NCIC Clinical Trials Group (NCIC-CTG) to start a Canadian clinical trial that may eventually include patients with glioblastoma across the country.

"Discovering new pathways and therapies that can be tested in the clinic provides the greatest hope for brain cancer patients and their families," said corresponding author Samuel Weiss, PhD, professor and director of the HBI.

Glioblastoma is the most common and deadly form of brain cancer among adults. The progression and complexity of the tumors are often difficult to treat. The median survival for patients is 15 months, with less than 5% of patients surviving beyond 5 years.

The researchers are now collaborating with other cancer researchers and the drug manufacturer AstraZeneca to plan a clinical trial testing a similar, but newer, drug related to AZD8055. The newer drug is called AZD2014, and it will be tested in combination with temozolomide in patients with glioblastoma.

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