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Choking Off Cancer
https://www.technologyreview.com/2002/07/01/234815/choking-off-cancer/

Today’s cancer drugs are notorious for killing healthy cells along with cancerous ones. A new anticancer approach could offer a more precise option: kill just the tumor by choking off its blood supplies. The first drugs based on this approach are now in human trials and, if they work, could provide a virtually side-effect-free means of fighting a host of cancers.

Called vascular targeting agents or antivascular therapies, the new drugs block the blood vessels that carry oxygen and nutrients to tumors. “Basically, it starves the tumor cells to death, so you get a massive amount of tumor-cell kill,” says Dai Chaplin, chief scientific officer at Watertown, MA-based Oxigene. This is in contrast to conventional chemotherapies, which kill cancer cells directly, and to another experimental approach called “anti-angiogenesis,” in which drugs stop new tumor blood vessels from growing.

Oxigene, Aventis and AstraZeneca are each testing vascular targeting agents in humans. These drugs bind to a protein called tubulin, preferentially targeting the tubulin in the cells that line the interior of tumor blood vessels. Long chains of the protein normally form an internal scaffold that helps keep these cells flat. The binding disrupts the scaffolding, and “the cells become fat and podgy and obstruct the blood flow through the tumor,” says vascular-targeting pioneer Phil Thorpe, a professor of pharmacology at the University of Texas Southwestern Medical Center. This effect can be seen within hours after injection of the drug.

So far, researchers have seen very few side effects in human tests, though a number of patients have felt pain in their tumors. And binding to tubulin is short-lived-on the order of hours-long enough to halt tumor blood flow but not long enough to kill normal cells, Thorpe says. “These drugs seem inherently safer than the blanket anticancer drugs that are currently available,” he notes.