No Resistance to Anticancer Agent

Cancer chemotherapy often fails because the tumors eventually become invulnerable to even the most potent drugs. But animal studies described in tomorrow's Nature suggest that the rapidly mutating cells do not develop resistance to a recently discovered protein that blocks the growth of the blood vessels tumors need to survive. Experts say the protein--if it works in humans--could eventually help doctors choke off and kill resistant tumors.

Earlier this year, researchers at Harvard Medical School in Boston reported finding the naturally occurring protein, called endostatin, which promised to shrink tumors without triggering resistance (ScienceNOW, 23 January). The trick? Instead of attacking cancer cells directly, endostatin stops the growth of new blood vessels that supply tumors with the oxygen and nutrients they need to grow.

Now, the same team--led by Thomas Boehm and Judah Folkman-has confirmed that repeated doses of endostatin remain potent. In the yearlong trial, mouse lung, skin, and bone tumors grew continuously when left untreated. Treatment with conventional chemotherapies kept the tumors in check for less than 2 months before resistance cropped up, soon after leading to the death of the mice. In contrast, the tumors never lost their susceptibility to endostatin. They shrank to barely visible after each of up to six injections. Some tumors, in fact, appeared to stay permanently shrunken and dormant after just two treatments, allowing the mice to gain weight for up to 6 months, when they were killed for study.

The results "are unprecedented and could herald a new era of cancer treatment," says Robert Kerbel of the University of Toronto in Canada. But he cautions that the findings need to be replicated with other cancers and in humans. And even if that can be done, Michael O'Reilly, a member of the Harvard team, notes that endostatin or similar treatments will probably have to be given in conjunction with conventional cancer cell-killing therapies to be effective. "The new approach could hold tumors in check," he says, "but probably won't knock them out completely."

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