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Pincer movement

发布时间:2019-03-07 08:10:12来源:未知点击:

By Andy Coghlan A SIMPLE molecule not only stops tumours spreading, it also limits their blood supply. And because it targets cancers with precision, it promises to cause fewer side effects than similar anticancer treatments. The molecule, a circular peptide comprising just 10 amino acids, owes its precision to the fact that it binds to two enzymes produced exclusively by tumour cells and growing blood vessels. The target enzymes, called gelatinase A and gelatinase B, help tumour cells to burrow through structural tissue and the linings of blood vessels. This allows them to escape from their original site, migrate through the bloodstream and seed secondary tumours elsewhere. Once cancer has spread in this way, it becomes much harder to treat. By neutralising the enzymes, the peptide also blocks the formation of new blood vessels, which are vital for nourishing tumours. In this way it delivers a double blow to a tumour, stopping its cells from spreading and limiting its supply of nutrients. “It gets to the site where you want it, then blocks the enzymes as well,” says Renata Pasqualini, head of the team that developed the peptide at the Burnham Institute in La Jolla, California, part of the US National Institutes of Health. She and her colleagues expect the peptide to have much less damaging side effects than similar experimental drugs that indiscriminately neutralise all matrix metalloproteinases, the family of enzymes that break down the bonds between cells and to which gelatinase A and B belong. In a series of collaborative experiments with Finnish researchers at the University of Helsinki, Pasqualini and her colleagues showed that mice implanted with three types of human tumour survived longer if treated with the peptide. The tumours stopped growing and sprouting vessels (Nature Biotechnology , vol 17, p 768). Pasqualini is confident that the peptide will work against many types of cancer. “There are data showing that virtually all tumour cells produce the two enzymes, and the more aggressive the tumours, the more they produce,” she says. In further tests on animals, she hopes to establish the most effective dose and the optimum stage at which to treat cancers. The researchers are also developing variants of the original peptide that last longer in blood. Pasqualini and her entire team are due to move next month to the M. D. Anderson Center in Houston, Texas, to prepare for clinical trials. In the same issue of Nature Biotechnology (p 749), Judah Folkman of Harvard Medical School in Boston, who also researches blood vessel suppressing drugs, describes the peptide breakthrough as a major step. Folkman says that the peptide could not only be used as a drug in its own right,