Picky. A peptide latches onto receptors on the lining of a prostate blood vessel (top), but doesn't appear on the skin (bottom).

A New Angle on Targeted Drug Design

Staff Writer

A rare experiment with a brain-dead man has added weight to the notion that blood vessels in different parts of the body are distinct. A team of biologists infused 1 billion different peptides into the man to determine which blood vessels they traveled to. Their findings hint at the possibility of designing cancer drugs that target specific tissues.

Whereas cancers are often localized in specific tissues, drugs to treat the disease are rarely so selective. One solution might be to exploit differences in the molecular signatures of blood vessels that nourish tumors in various parts of the body. For example, a drug designed to target peptides--small chains of amino acids--in the linings of tumor-feeding vessels in the liver could choke off a tumor's blood supply without affecting healthy tissues in the rest of the body. But scientists are only beginning to identify which peptides home in on which blood vessels in mice, and some worry those results may not translate to humans.

Wadih Arap and Renata Pasqualini, a husband-and-wife team of cancer biologists at M. D. Anderson Cancer Center in Houston, Texas, learned about a brain-dead 48-year-old man in the hospital's Intensive Care Unit. The man's family had wanted to donate his organs, but his advanced cancer made that impossible. Instead, the family agreed to let Arap and Pasqualini infuse their entire library of peptides into the man's body. The study underwent ethical reviews by several groups before being approved.

Before the man was taken off life support, the researchers collected samples from his muscle, skin, bone marrow, prostate, and fat. They then sequenced hundreds of peptides from each type of tissue. To double-check that the injected peptides were choosy about the tissues they bound to--a key feature if they're to be useful therapeutically--the team focused on a peptide that turned up in prostate blood vessels. This peptide bound well to prostate tissue, but not to samples from skin. The reverse was true for a peptide found on skin blood vessels, they report in February's issue of Nature Medicine.

By attaching a specific peptide known to migrate to certain blood vessels to a cancer-killing medication, you can "get your smart drug to a particular site," says Bruce Zetter, a cancer biologist at Children's Hospital in Boston. The work holds great promise, he says, but it may move slowly until experiments with brain-dead patients gain greater acceptance among clinicians.

Related sites

Renata Pasqualini's home page
Wadih Arap's home page
Background on angiogenesis

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