Mayo Clinic discovers wood mold toxic to Multiple Myeloma

ROCHESTER, Minn. -- Mayo Clinic Cancer Center (http://cancercenter.mayo.edu/) 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 are available online in the March 15 issue of Blood (http://bloodjournal.hematologylibrary.org/).

"This research is only the beginning," says Keith Bible, M.D., Ph.D., oncologist and the study's primary investigator. "But we are very hopeful that chaetocin may some day provide needed help to our patients."

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

"There were a number of fascinating findings," says Crescent Isham, Mayo Graduate School student and lead author of the study. "In addition to observing many favorable aspects of chaetocin, we discovered some avenues for further research into other possible anti-myeloma agents." She says 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 Dr. Bible. "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." It will still be a few years before patient trials can commence, he says.

Mayo Clinic has a long tradition of leadership in myeloma research and novel therapeutic development, with the oldest and largest myeloma program in the country. 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.

Other researchers contributing to this study included Jennifer Tibodeau, Ph.D.; Wendy Jin; Ruifang Xu, M.D., Ph.D.; and Michael Timm. Funding for this research came from the National Institutes of Health and the Multiple Myeloma Research Foundation.

More information on hematology research at Mayo Clinic Cancer Center can be found on the Hematologic Malignancies Program (http://cancercenter.mayo.edu/mayo/research/hematologic_malignancies/index.cfm) Web site.