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For more than two decades, researchers have tried to develop a light-activated cancer therapy that could replace standard chemotherapy, which is effective but causes serious negative side effects. Despite those efforts, they’ve struggled to come up with a light-activated approach that would target only cancer cells.

Now scientists at the National Cancer Institute have developed a possible solution that involves pairing cancer-specific antibodies with a heat-sensitive fluorescent dye. The dye is nontoxic on its own, but when it comes into contact with near-infrared light, it heats up and essentially burns a small hole in the cell membrane it has attached to, killing the cell.

To target the tumor cells, the researchers used antibodies that bind to proteins that are overexpressed in cancer cells. “Normal cells may have a hundred copies of these antibodies, but cancer cells have millions of copies. That’s a big difference,” says Hisataka Kobayashi, a molecular imaging researcher at the National Cancer Institute and the lead author of the new study, published this week in Nature Medicine. The result is that only cancer cells are vulnerable to the light-activated cascade.

The researchers tested the new treatment in mice and found that it reduced tumor growth and prolonged survival.

There are a few kinks to work out before the system can be adapted for humans, though. For instance, the researchers couldn’t test the treatment’s effect on large tumors, since killing off too many cells at once caused cardiovascular problems in the mice. Finding the right cancer-cell markers to pair with the dye may also prove difficult. For example, HER-2, one of the proteins targeted in the study, is only expressed in 40 percent of breast-cancer cells in humans.

Still, the lack of toxicity associated with the treatment is a huge advantage, says Karen Brewer, a chemist at Virginia Tech who also works on light-activated cancer therapies. “What’s interesting about this study is that they’re applying a traditional method of targeting cancer cells to a light-activated treatment,” she says. “This is really where the field is headed.”

The dye used in the study offers another bonus because it lights up—allowing clinicians to track the treatment’s progress with fluorescence imaging. In the mice, the fluorescence visibly declined in tumor cells a day after administration of the near-infrared light. Kobayashi suspects the approach could also prove valuable as a secondary therapy by helping surgeons label cancer cells that may remain after a tumor has been excised. “It could help clean up the tumor cells that are harder for surgeons to get to,” he says.

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Credit: Hisataka Kobayashi, National Cancer Institute

Tagged: Biomedicine, cancer, imaging, cells, chemotherapy, fluorescence

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