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'Smart drug' targets deadly brain cancer

A study led by Mayo Clinic researchers and conducted by the North Central Cancer Treatment Group (NCCTG) reports that a new "smart" drug treatment for an incurable form of recurrent brain cancer slowed tumor growth in more than one-third of the 65 adult patients who tried it. The same research team also developed a screening technique to help predict which patients will respond best to this treatment.

Mayo researchers will present these findings at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla. The NCCTG study addressed the most common kind of tumor arising from brain tissue of adults, glioblastoma mutiforme. Current treatment outcomes for this type of cancer are extremely poor: median patient survival is 12 to 16 months, and recurrent disease has a dismal prognosis. The World Health Organization categorizes fast-growing glioblastoma multiforme as a grade IV cancer.

Significance of the Mayo Clinic/NCCTG Research

This discouraging prognosis may change as a result of the rational foundation for new therapies the NCCTG research provides. Study data showed that in 36 percent of patients suffering from recurrent glioblastoma multiforme, the new "smart" drug behaved as hypothesized: It found its target -- tumor cells -- and actively worked against them to slow tumor growth.

According to the study's lead investigator, Mayo Clinic medical oncologist Evanthia Galanis, M.D., "Treatment was well tolerated, and imaging responses were observed in a significant portion (36 percent) of patients with recurrent glioblastoma multiforme participating in this study -- which is a high response rate for this very resistant disease. These early results suggest that we are on to a promising new treatment strategy that could potentially help us improve treatment for patients with recurrent glioblastoma."

Achieving the 36 percent regression rate was an encouraging result -- but researchers didn't stop there. They t ook the work a step further by analyzing specific tumor properties of the patients enrolled in the study. What they found is also encouraging. Patients most likely to respond well to the drug shared a common feature -- activation of a specific tumor protein, p70s6 kinase, which is closely associated with the drug target molecule.

Knowing that this protein is a key player in the chain of events that determines drug activity could be useful in screening patients to help determine the best candidates for the drug. Says Dr. Galanis, "This could allow us to customize drug administration to the patients most likely to benefit from it, and in that way, improve care."

A Smart Drug

In their study, NCCTG researchers used an investigational drug that is not currently available for wide use. Known as CCI-779, or temsirolimus, it is a "smart" drug in the sense that it has been designed to target specific changes in the glioblastoma multiforme tumor cells that previous studies have identified as key factors in the tumor's aggressive behavior.

About Glioblastoma Multiforme

In adults, glioblastoma multiforme is the most common form of brain tumor. Because it originates in the brain, physicians refer to it as a primary tumor. This is in contrast to a tumor that develops in the brain from cancer cells that have spread from tumors elsewhere in the body. Glioblastoma multiforme accounts for more than 50 percent of the estimated 18,000 primary malignant brain tumors diagnosed each year in the United States. When first diagnosed, glioblastoma multiforme is usually treated with surgery, radiation therapy and chemotherapy -- and median survival is 12 to 16 months. For patients in whom the disease recurs, the prognosis is indeed dismal: there are no good treatment options.

The Next Step

Mayo Clinic researchers are continuing to investigate the implications of their findings. NCCTG studies now under way will test the combination of CCI- 779 with radiation therapy in patients who have newly diagnosed glioblastoma multiforme. They will also test CCI-779 in combination with other targeted therapies in patients with recurrent cases of glioblastoma multiforme.

Collaboration and Support

In addition to Dr. Galanis, Mayo Clinic research team members included Jan Buckner, M.D.; Matthew Maurer, M.S.; Brad Erickson, M.D., Ph.D.; Bernd Scheithauer, M.D.; Robert Jenkins, M.D., Ph.D.; and Karla Ballman, Ph.D. External collaborators included researchers from Johns Hopkins University and the University of Texas, San Antonio.


Source:Mayor Clinic

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