ORLANDO, Fla. -- Researchers at Mayo Clinic Cancer Center, in cooperation with industry partners, have, for the first time, identified tumor specific alterations in the cellular pathway by which the multiple myeloma drug bortezomib (Velcade) works, and they have identified nine new genetic mutations in cancer cells that should increase a patient's chance of responding to the agent.
The investigators say these findings, presented Sunday, Dec. 10, at the 2006 American Society of Hematology Annual Meeting in Orlando, may help physicians tailor treatment to patients with multiple myleoma, a difficult-to-treat cancer of plasma cells that is the second most common blood cancer in the United States.
"Bortezomib seems to work in about one-third of patients who use it, but we have not been able to predict which ones," says the study's lead author, Leif Bergsagel, M.D., a hematologist at Mayo Clinic 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.
"Now that we know the pathway the drug targets, and genetic mutations within this pathway that make patients respond better, we are working on a simple way to select those patients who are the best candidates for use of bortezomib," says Dr. Bergsagel.
In 2003, after only a four-month review, the Food and Drug Administration (FDA) approved use of bortezomib in patients who have failed other treatments for multiple myeloma. Later studies showed it lengthened survival by as much as six months. The drug was the first approved in a new class of agents known as proteasome inhibitors. Proteasomes are large protein groups inside cells that break down other proteins. Agents that inhibit the proteasome cause a buildup of proteins that affect many signaling cascades (various necessary biological processes). Bortezomib was initially thought to exert its activity by disrupting one of two k
Contact: Elizabeth Zimmermann