Oncology Central

Glioblastoma animal studies result in trial of potential new combination therapy

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Researchers from the University of Calgary’s Hotchkiss Brain Institute and Southern Alberta Cancer Research Institute (both Canada), led by Samuel Weiss, have discovered a potential new drug combination therapy for glioblastoma patients. As a result of the work, which was published last week in Clinical Cancer Research, Phase I/II clinical trials are due to begin in patients early in 2015.

Glioblastoma is the most aggressive form of brain cancer. It is a challenging disease to treat due to the complexity and progression of tumors, and currently the median survival for patients is 15 months.

Researchers took brain tumor-initiating cell lines from 100 different glioblastoma patients and inserted them into animal models, which were then utilized to investigate the effectiveness of drug combinations against the disease. The results demonstrated that combining temozolomide, which is already given to most glioblastoma patients, with another drug termed AZD8055 increased the life expectancy of the animals 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,” explained Artee Luchman from the university’s Cumming School of Medicine and a member of the Hotchkiss Brain Institute.

The team discovered that AZD8055 therapy inhibited the mTOR signaling pathway in the brain tumor-initiating cells and, when combined with the standard therapy, caused more cancer cells to die. The elucidation of this mechanism is important as it could lead to new drug discoveries in the future.

The researchers are now collaborating with other investigators and drug manufacturer AstraZeneca to plan a Canadian clinical trial testing a similar, but newer, drug related to AZD8055 (termed AZD2014) in combination with temozolomide in patients with glioblastoma.

“Discovering new pathways and therapies that can be tested in the clinic provides the greatest hope for brain cancer patients and their families,” commented Weiss.

Source: Luchman HA, Stechishini O, Nguyen SA, Lun XQ, Cairncross JG, Weiss S. Dual mTORC1/2 Blockade Inhibits Glioblastoma Brain Tumor Initiating Cells In Vitro and In Vivo and Synergizes with Temozolomide to Increase Orthotopic Xenograft Survival. Clin Cancer Res doi: 10.1158/1078-0432.CCR-13-3389 (2014); The Hotchkiss Brain Institute press release

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