Avoid relapse of AML

Researchers have made a small molecule that could deliver a one-two punch to proteins that resist chemotherapy in patients with AML. The researchers are from Rice University, Baylor College of Medicine and the University of Texas MD Anderson Cancer Center. It may be the key to helping patients who are fighting acute myeloid leukemia (AML) avoid a relapse.

The work led by Rice chemist Zachary Ball, Baylor pediatrician Michele Redell and MD Anderson oncologist David Tweardy appears this week in the journal Angewandte Chemie.

The protein STAT3, interferes with chemotherapy by halting the death of cancerous cells and allowing them to proliferate. The molecule locates and attacks a previously unknown binding site on STAT3, thus disrupting its disease-promoting effects.

The STAT3 protein stands for "signal transducer and activator of transcription 3". It is a suspected factor in the relapse of nearly 40 percent of children with AML. The new proximity-driven rhodium(II) catalyst known as MM-206 finds and modifies an inhibitor-binding site on the protein's coiled coil -- literally protein coils coiled around each other -- and delivers the inhibitor, naphthalene sulfonamide, to the modified site.

"We know that increased activity of STAT3 in AML and other cancers helps the cancer cells survive chemotherapy, so any new strategy we can develop to stop that process could mean real benefit for our patients," said Redell, who is also part of the leukemia and lymphoma teams at Texas Children's Hospital.

"Our main advance, from a medicinal perspective, is that this compound also works in a mouse model," Ball said. "All the other compounds worked in cells, but in mice, they weren't potent enough or stable enough."

Follow-up studies should lead to improved versions of the complex. The new discovery is of great importance showing the way to future anti-cancer approaches.

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