"Starting with the basic migrastatin molecule, we cut a piece there, add a piece here," he explained, "and what we ended up with were two compounds -- core macroketone and core macrolactam -- that are about 1,000 times more powerful at inhibiting cancer cell migration."
In fact, in a mouse model, the analogues were between 91 to 99 percent effective in stopping the spread of breast cancer cells, the researchers report. Cell culture studies suggest they can reproduce that success in a wide range of other cancers, too.
"What's unique about these analogues is that they do all this without affecting primary tumor cells, or their blood supply," Dr. Huang said. "To our knowledge, that's a real first."
Exact mechanisms remain unclear.
"Obviously, these compounds are targeting some step in the cell-migration process," Dr. Huang said. The activity of a migration-linked protein called Rac appears to be much reduced in cancer cells affected by the analogues, and the researchers also noticed that malignant cells failed to grow tiny "antennas," called lamellipodia, another crucial step in the migration process.
"Therefore, the migrastatin analogues must be working on something upstream of those two important steps," Dr. Huang said.
Dr. HuangÕs next important step is moving these analogues into clinical trials.
"We're trying right now to get a company interested in this, especially because the mice used in our trial seemed to experience minimal toxicity -- a good sign that patients might tolerate these compounds, too," Dr. Huang said.
"It's all very exciting," he said. "Metastatic disease is such a tough problem, and these compounds could provide patients with a brand new kind of hope."