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"At the time, I didn't really know anyone who'd been touched by cancer," the 57-year-old Barter told reporters at a special meeting held Monday in Boston, co-sponsored by Dana-Farber and the National Cancer Institute (NCI).
His fight soon became much more personal, however.
A year after that first bikeathon, Barter's 3-year-old son was diagnosed with retinoblastoma. The boy survived, but at the cost of losing an eye.
Then, four years ago, Barter himself was diagnosed with the deadly blood cancer multiple myeloma.
He turned to experts at Dana-Farber's Jerome Lipper Multiple Myeloma Center for help. Center director Dr. Kenneth Anderson placed him on Revlimid, an easily tolerated, thalidomide-like drug that targets both the myeloma cell and the bone marrow "microenvironment" in which it lives.
"I've been on it for three years," said Barter, who owns an environmental testing lab in Berlin, Mass. "I'm in remission, and I feel great."
Revlimid is just one of a new generation of targeted therapies revolutionizing the treatment of multiple myeloma -- a lethal blood cancer that affects immune plasma B-cells residing in the marrow. According to the NCI, more than 15,000 Americans are diagnosed with multiple myeloma each year.
Just last week, Anderson's team announced in the New England Journal of Medicine that a new drug, bortezomib (Velcade), was able to greatly extend the survival of multiple myeloma patients who had failed previous therapies. Velcade works by inhibiting the activity of the proteasome, a type of cellular "garbage disposal" responsible for chopping up and clearing away misfolded or mutated proteins that accumulate naturally in cells. Without a functioning proteasome, the tumor cell dies.
But cancer is tricky, rapidly mutating around each new drug science throws its way. That's why Anderson's lab is already developing a third medication aimed at another cellular regulator, the aggresome.
The Boston researchers discovered that highly active cancer cells favor this secondary protein-removing apparatus -- especially when the proteasome is under threat from drugs such as Velcade.
"It's an additional, alternative system to the proteasome," explained Anderson, who is also a professor of medicine at Harvard Medical School. "Our recent pre-clinical studies found that if you inhibit the proteasome with Velcade, the myeloma cell cranks up the activity of the aggresome system instead. Conversely, if you block the aggresome system's function, the cancer cell turns on the proteasome. So our new strategy is to inhibit both of them."
Reporting in last week's issue of the Proceedings of the National Academy of Science, the Dana Farber team announced success in the laboratory at suppressing aggresome function using a newly designed molecule called tubacin.
At the same time, they used Velcade to clog up the proteasome.
"Inhibiting both of these systems seems very effective at overcoming the cell's ability to dispose of all this junk protein," Anderson said. As this cellular junk piles up, malignant cells have no choice but to self-destruct, he added.
The Boston researcher said his team is already testing tubacin in animal models while seeking out a more specialized, tubacin-like compound for use in clinical trials.
The aim is to hit myeloma with a one-two-three punch, leaving malignant cells no room for escape.
Already, studies are showing that Velcade and Revlimid in combination "are even more effective [than either drug alone] because of their enhanced cancer-cell killing power," Anderson said. The combination of these two drugs also "overcomes problems of drug resistance while being used at lower doses," he added.
"The model for all this are infectious diseases like tuberculosis or HIV, where we know that with a cocktail of drugs you truly can overcome resistance," Anderson said. "We think that will translate to cancer as well. Ultimately, you need a team to win."
"Dr. Anderson tells me there are many more options and other drugs coming down the pike," he said. "That if, for some reason, Revlimid does stop working, we have other things we can try. And I'm ready."
SOURCES: Terence Barter, Berlin, Mass.; Kenneth Anderson, M.D., Kraft Family Professor of Medicine, Harvard Medical School, and director, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston; June 20, 2005, presentations, co-sponsored by Dana-Farber Cancer Institute/National Cancer Institute, Boston; June 14, 2005, Proceedings of the National Academy of Sciences
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