Chaetocin shows promise as a new anti-myeloma agent

Mayo Clinic Cancer Center researchers have found that chaetocin, a by-product of a common wood mold, has promise as a new anti-myeloma agent. Results of their study, being presented today at the American Association for Cancer Research annual meeting, show the by-product to be more effective than currently used therapies at killing multiple myeloma cells.

The complete findings are also available online in Blood.

"There were a number of fascinating findings," says Keith Bible, M.D., Ph.D., oncologist and the study's primary investigator. "In addition to observing many favorable aspects of chaetocin, we discovered some avenues for further research into other possible anti-myeloma agents."

Multiple myeloma is an incurable bone marrow cancer that kills more than 11,000 people each year in the United States, reports the American Cancer Society. Dr. Bible's team has shown for the first time that chaetocin has promising anti-myeloma activity. They found that chaetocin's promise includes the ability to:

• Kill myeloma cells harboring a diverse array of genetic abnormalities
• Cause biological changes and induce oxidative stress in myeloma cells, leading to their death
• Selectively kill myeloma cells with superior efficacy to commonly-used anti-myeloma drugs including dexamethasone and doxorubicin
• Reduce myeloma growth in mice
• Rapidly accumulate in cancer cells

The researchers were surprised that chaetocin, while structurally similar to anti-cancer agents known as histone deacetylase inhibitors (HDACIs), did not, at cytotoxic concentrations, seem to function as an HDACI; but instead that the cytotoxic mechanism appeared to be at least in part attributable to oxidative stress caused by chaetocin.

"Much more research needs to be done," says Jennifer Tibodeau, Mayo post-doctorate fellow and presenter of the study, "but we are hopeful that chaetocin may some day provide needed help to our patients."

Dr. Bible indicated that it will still be a few years before patient trials can commence, but says, "we will continue working with chaetocin to find the best way to use it for our patients. We are also pursuing other agents which may cause similar cellular oxidative stress."

With the oldest and largest myeloma program in the country, Mayo Clinic has a long tradition of leadership in myeloma research and novel therapeutic development. Dr. Bible's research is part of an ongoing initiative within Mayo's Dysproteinemia and Myeloma Groups to find promising natural or man-made agents for the treatment of myeloma and other blood diseases and to investigate at a basic science level and subsequently translate that research into clinical practice