Drug shows potential to treat some cases of multiple myeloma

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Multiple myeloma blood cancer treatment

Certain patients suffering from multiple myeloma, a difficult-to-treat cancer of the plasma cells, may respond positively to a drug that shows potential to extend their survival rates by as much as six months, according to researchers at the Mayo Clinic Cancer Center.

For the first time, Mayo researchers have identified tumor-specific alterations in the cellular pathway by which the multiple myeloma drug, bortezomib (Velcade), works, as well as nine new genetic mutations in cancer cells that should increase a patient's chance of responding to the agent.

Bortezomib seems to work in about one-third of the patients who use it, but it has been difficult to predict which ones, according to the study's lead author, Leif Bergsagel, M.D., a hematologist at Mayo Clinic in Arizona. "We now have identified a group that will likely respond, because these nine mutations seem to be present in at least 25 percent of newly diagnosed patients," he said.

The findings were presented earlier this week at the 2006 American Society of Hematology Annual Meeting in Orlando.

"Now that we know the pathway the drug targets - and genetic mutations within the pathway that make patients respond better - we are working on a simple way to select patients who are the best candidates for use of bortezomib," Bergsagel added.

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In 2003, following only a four-month review, the Food and Drug Administration (FDA) approved use of bortezomib (part of a class of agents known as proteasome inhibitors) for patients who failed to respond to other treatments for multiple myeloma. Later studies showed it lengthened survival by as much as six months.

Then, through extensive genetic examination of 42 unique multiple myeloma cells and tumor samples taken from 68 patients, mutations were discovered that make the tumor more susceptible to bortezomib treatment, explains the study's senior author, Rafael Fonseca, M.D., also at Mayo Clinic in Arizona.

"Identifying these mutations in patients will help us decide who should be treated with bortezomib - probably as an initial therapy," adds Fonseca.

Now that the mutations have been identified, drug designers may be able to fashion therapies that are more specific to these genetic alterations and, therefore less toxic, according to Bergsagel. "These mutations represent good targets for drug development."

This type of drug design is typical of the innovations that are emerging in individualized medicine - when knowledge of the molecular structure of cancer cells, for example, help identify the most effective treatment options for an individual patient.

Multiple myeloma is the second most common blood cancer in the U.S.

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