Antibiotic treatment for leukemia
By Tyler Irving
Posted February 2012
Even with chemotherapy, acute myeloid leukemia (AML) kills more than half of those afflicted. Now, researchers from the Ontario Cancer Institute (OCI) have identified an antibiotic molecule that could also work as an AML therapeutic.
The team, led by OCI’s Aaron Schimmer, assembled a list of 500 compounds already approved as drugs by the U.S. Food and Drug Administration (FDA). They then used a high-throughput screen to test them for effectiveness against both lymphoid and myeloid leukemia stem cells. A prime candidate emerged in the form of tigecycline, an antibiotic normally used to treat skin and abdominal infections.
As an antimicrobial agent, tigecycline is known to inhibit bacterial protein synthesis by binding to their ribosomes. In human cells, mitochondria have their own ribosomes that are similar to those found in bacteria. “We demonstrated that in leukemia cells, tigecycline is inhibiting mitochondrial protein synthesis, which ultimately causes cell death by depriving them of an energy source,” says Schimmer.
Leukemia cells have greater mitochondrial mass and a greater dependence on this energy source. This makes them more sensitive to this type of disruption and allows tigecycline to selectively kill leukemia cells without destroying normal ones. “Inhibiting mitochondrial protein synthesis would really be a first-in-class therapy for leukemia,” Schimmer says. Schimmer and his colleagues have already started a Phase 1 trial, but he cautions that the formulation, dose and schedule have yet to be optimized. Additionally, Schimmer believes it’s possible that chemists could design tigecycline analogues that would be more potent or more selective of mitochondrial ribosomes over bacterial ones. “That’s something we’re actively engaged with.” The research is published in Cancer Cell.
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