MSUToday
Published: May 26, 2016

MSU researcher working to develop new cancer-fighting drug

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Michigan State University professor and researcher André Bachmann is collaborating on cancer-fighting research that could change the way we treat the illness.

Bachmann, professor of pediatrics and associate chair for research in the MSU College of Human Medicine’s Department of Pediatrics and Human Development, is working with plant biologist Robert Dudler from the University of Zurich to develop a natural bacterium produced chemical with anti-cancer properties.

Dudler originally found the substance, called syrbactin, or syringolin A, and together Dudler and Bachmann tested it and found that it appeared to kill cancer cells, but could not explain why.

In 2008, Bachmann, Dudler and seven other researchers published a study in the international science journal Nature, revealing that syrbactin is a “proteasome-inhibiting drug” that kills cancer cells by interrupting their ability to digest proteins.

Bachmann is the lead author of a follow-up study in the April issue of The Journal of Biological Chemistry, revealing that a synthetic and slightly modified version of syrbactin, called TIR-199 killed multiple myeloma and neuroblastoma cells and possibly could be effective in preventing the spread of other kinds of cancers.

“I’m very excited about it,” Bachmann said, although he indicated that many years of further research lie ahead before some variation of TIR-199 may be tested in human clinical trials.

Getting TIR -199 to human clinical trials will require the continuing collaboration of academic researchers from different scientific disciplines, significant research funds through federal or foundation grants and support from and collaboration with the pharmaceutical industry.

“This is a study that combines chemistry and cancer biology,” Bachmann said. “That’s the beauty of this — the collaboration. It’s a very complementary interaction between the two sciences.”

A co-author of the latest study is Michael Pirrung, an organic chemist in the University of California’s Department of Chemistry, who altered the molecular structure of syrbactin to create TIR-199, which proved to be more effective than syrbactin.

Proteasomes can be compared to an office paper shredder. As protein enters cancer cells, the proteasome cuts it into shreds, allowing the cells to grow and spread. As a proteasome inhibitor, TIR-199 interrupts that process, causing the cancer cells to die, Bachmann said.

In laboratory tests, TIR-199 killed multiple myeloma cells, a cancer of the blood’s plasma cells. It also appeared to be somewhat effective against neuroblastoma, a highly aggressive childhood cancer that forms on nerve cells. In tests by the National Cancer Institute, or NCI, TIR-199 “showed strong activity against kidney cancer,” Bachmann said. “That made them very interested in this compound, and we continue to work with the NCI to further evaluate the compound.”

Before human clinical trials can begin, Bachmann expects he and the other researchers will spend years tweaking the molecular structure of TIR-199, hoping to improve its cancer-fighting abilities while reducing potential side effects. Ultimately, the chemical that emerges could be used in combination with other drugs to stop cancer by hitting multiple targets.

“Is it as good as it can get?” Bachmann asked. “No, it can get better. I think we need several rounds of modifications before we can in the far future consider clinical trials. It’s not the final version, but we’re on the right track.”

Andre Bachmann, professor of pediatrics and associate chair for research in MSUís College of Human Medicineís Department of Pediatrics and Human Development.

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