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UA team uses genetics to tackle brain cancer

Michael Hammer, Ph.D. (left), and Baowei Chen, Ph.D., examine cells in which the WIF-1 gene is silenced. (Kris Hanning)

Glioblastoma is a deadly brain cancer that grabbed headlines for claiming the lives of Sens. Edward Kennedy and John McCain. Michael Hammer, Ph.D., and a team of University of Arizona researchers have discovered that the disease could be “tricked” into sparing more of its victims.

The researchers looked for genetic differences between glioblastoma cells from long- and short-term survivors to discover that those who survived longer had a protein that might be targeted to increase survival in all glioblastoma patients. The results were presented in November at the Society for Neuro-Oncology conference in New Orleans. This work is in its early stages, and the researchers say they are many years and millions of dollars away from potential translation into treatments for patients.

“I was curious to know how genes are differentially expressed in patients who live longer,” says Hammer, co-director of the UA Cancer Center Genomics Shared Resource and research scientist with the UA BIO5 Institute. “If we can identify a pathway in the tumor that we might be able to target, we can try to make the short-lived patients look more like the long-lived patients.”

“Glioblastoma essentially is incurable,” says Baldassarre “Dino” Stea, M.D., Ph.D., head of the UA College of Medicine–Tucson Department of Radiation Oncology. “In the past 15 years, only one drug — temozolomide — has been invented, whereas the rest of the cancer field is zooming forward.”

With surgery, followed by chemotherapy and radiation, adults with glioblastoma survive for an average of 11–15 months. Some succumb sooner, while others outlive their initial prognosis by months or even years.

After sifting through 800 genes in 23 glioblastoma samples, the team identified the WIF-1 gene, which manufactures the WIF-1 protein, a strong predictor of long-term survival.

Hammer also is known for the DNA Shoah Project, established with New York-based geneticist Syd Mandelbaum. The databank helps descendants of Holocaust victims make genetic matches to recovered remains.

In addition, he collaborated with Rabbi Yaakov Kleiman, director of the Center for Kohanim in Jerusalem, on research on the “Cohen gene,” tracing the Jewish priestly lineage from Moses’ brother, Aaron, to modern times.

While testing for the WIF-1 gene someday may help oncologists predict which patients will survive longer, a greater hope is that this work will lead to a drug that targets glioblastoma tumors with more precision than standard treatment.

“We hope to create a drug to suppress the Wnt pathway so that everybody survives longer,” Stea says. “It would be the pot of gold at the end of the rainbow.”

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