New potential treatment breakthrough for advanced brain cancer
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New potential treatment breakthrough for advanced brain cancer

Doctors at UCLA, Cleveland Clinic, University of California San Diego School of Medicine and additional institutions have achieved a milestone in the development of a treatment for people with recurrent glioblastoma, the most common and aggressive form of brain cancer, by successfully demonstrating a modified virus that can extend the lives of patients with the disease. Among the team a Greek Neurosurgeon, Dr Steven Kalkanis.

The results of the study were published on June 1 in the journal Science Translational Medicine.

Steven Kalkanis is the Chairman of the Department of Neurosurgery and Co-Director at the Neuroscience Institute at Henry Ford Health System. He received his medical degree from Harvard Medical School.

Glioblastomas are the most deadly of all brain cancers. If the tumor recurs following chemotherapy and radiation, there are very few treatment options left, and patients have only months to live.

In a phase I multi-center clinical trial, the researchers found that, of the 43 participants who were given the investigational treatment Toca 511 and Toca FC, overall survival increased to 13.6 months compared to 7.1 months for an external control. For some patients, survival was extended to more than two years with few side effects.

This year, the total number of newly diagnosed high-grade glioblastoma will be about 160,000 worldwide, including 14,000 in the United States. The new findings were led by Drs. Timothy Cloughesy, a member of the UCLA Jonsson Comprehensive Cancer Center and director of the UCLA neuro-oncology program, and Michael A. Vogelbaum, professor of neurosurgery and associate director of the brain tumor neuro-oncology center at the Cleveland Clinic. Their work is the first publication of clinical data involving this new type of modified virus known as a retroviral replicating vector (RRV). RRVs can deliver a gene with a specific function to a cancer cell, and insert it, thereby debilitating the cell. The use of RRVs shows tremendous promise in the development of innovative new therapies for all types of brain cancer.
“For the first time, this clinical data shows that this treatment, used in combination with an antifungal drug, kills cancer cells and appears to activate the immune system against them while sparing healthy cells,” said Cloughesy, who is also a consultant for trial sponsor Tocagen, a private biopharmaceutical company. “This approach also has potential in additional types of the disease such as metastatic colorectal and breast cancers.”

During the first step of treatment the patient is given an injection of Toca 511, which is a modified virus that selectively infects actively dividing cancer cells and delivers a gene for an enzyme called cytosine deaminase (CD) to the cancer cells. As it spreads through the tumor, Toca 511 programs the cancer cells to make (CD). Once they do, the cancer cells are then ready for the second step of the treatment.

Next, the patient is prescribed oral cycles of Toca FC, an antifungal drug, for seven days, every four to eight weeks. The genetic changes created by Toca 511 allows infected cancer cells to convert Toca FC into the FDA-approved anticancer drug, 5-fluorouracil (5-FU). As a result, infected cancer cells and immunosuppressive cells are selectively killed, subsequently activating the immune system to recognize and kill cancer cells, while leaving healthy cells unharmed.
In other words, the therapies work together to attack brain cancer cells from the inside.

This study was performed in collaboration with investigators at New Jersey Neuroscience Institute, JFK Medical Center, Edison NJ; Moores Cancer Center, Department of Neurosciences, University of California- San Diego; Ohio State University Wexner Medical Center, Columbus, OH; Henry Ford Hospital, Detroit, MI; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami; Ribomed Biotechnologies, San Diego, CA; University of Arizona Cancer Center, Tucson, AZ; Cleveland Clinic Foundation, Cleveland, OH.
The study was mainly funded by Tocagen; several non-profit organizations, including Accelerate Brain Cancer Cure Foundation (ABC2), The National Brain Tumor Society, Voices Against Brain Cancer, the Musella Foundation, and the American Brain Tumor Association (ABTA) also supported the research.

 

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