June 19, 2000

Starving Cancer




Cutting Supply Lines


Not long ago, curing cancer seemed as unlikely as traveling at the speed of light. Now, an extraordinary treatment may be on the horizon. What's changed in the ongoing fight against cancer?

When researchers and health care professionals gathered last month in New Orleans, Louisiana, they had a chance to review the most promising breakthroughs in cancer therapy. And "angiogenesis inhibitors" may have been the most frequently spoken phrase at the conference.

For decades, doctors have tried to destroy life-threatening cancers with chemicals and radiation. Now the use of drugs that literally starve cancerous tumors may let cancer treatments succeed where others have fallen short.

The way in which cancerous tumors create new blood vessels around themselves—a process called angiogenesis—enables the tumors to grow and the cancer to spread. How to cut off these supply lines, with what are called "antiangiogentic drugs" or "angiogenesis inhibitors," has become a primary goal of cancer research. Medical researchers are confident that this new generation of drugs may stop cancers in areas such as the breasts, colon, and lungs.

Dr. Judah Folkman, of Children's Hospital Medical Center in Boston, Massachusetts, has pioneered this approach for the past 25 years. He explained how it works in a 1996 article for Scientific American magazine:

"Antiangiogenic therapy, in contrast to many other therapeutic approaches, does not aim to destroy tumors. Instead, by limiting their blood supply, it attempts to shrink tumors and prevent them from growing. Antiangiogenic drugs stop new vessels from forming around a tumor and break up the existing network of abnormal capillaries that feeds the cancerous mass."

  • Try explaining in your own words how these drugs can fight cancer.



Antiangiogenic therapy

From Theory to Practice  

Theory to PracticeFolkman's ideas about cancer and its treatment have electrified medical research with the promise of a cure to a disease long believed incurable. But coming up with a hypothesis is one thing. Developing drugs that are effective, safe, and available to anyone who needs them is another.

If you were to develop an idea for a cancer-fighting drug, what steps do you think you would have to take before making it widely available to the public?

Steps You Would Take
  • What particular medical problems would you be concerned with along the way?

A Long Road

The steps from medical theory to medical practice—and the problems that can develop along the way—are always a concern for researchers. In developing angiogenesis inhibitors and many other drugs, these researchers have had to follow a long road, with plenty of carefully planned stops along the way.

Studying the effects of new drug treatments on animals such as mice and rats can give scientists information on how effective and safe these treatments are without posing a risk to humans. Two years ago, Dr. Judah Folkman reported that he had stopped the growth of tumors in mice. His success greatly increased interest in angiogenesis inhibitors.

The researchers begin studies on humans.


Human Trials

Phase I Human Trials


Phase II Human Trials


Phase III Human Trials

This early stage of testing focuses on a small number of humans who have volunteered to receive the experimental treatments. (For all phases of human testing, researchers depend on volunteers who fit various criteria, such as degree of illness, age, and gender.) Researchers try to determine which way to administer the drug (orally, by injection, etc.); how frequently; and in what doses. Those conducting the trials also watch carefully for side effects.

The focus at this stage of testing an anticancer drug is whether it works on the cancer it is targeting. Again researchers work with a small group of human patients.

If the first two phases of a drug trial show promise, researchers move on to a larger number of patients, as many as several hundred. This phase compares the results of the new drug to other existing treatments. The patients are divided randomly into groups according to the particular treatment they receive. Researchers compare the effects of the different treatments in terms of which groups have better survival rates and fewer side effects.

Promising Results  

At this point, almost 20 clinical trials using angiogenesis inhibitors are underway around the world, and five have moved into Phase III trials. An estimated $4 billion has been spent researching the new drugs. At last month's New Orleans conference, sponsored by the American Society of Clinical Oncology, some of the findings gave cancer experts and patients reasons for optimism.

Because these drugs use proteins that are produced in the human body, there is less likelihood that they will produce the bad side effects common in radiation treatments and chemotherapy. Still, one study found that 6 of the 99 patients taking an antiangiogenesis drug experienced severe bleeding in the tumors being treated. Four of those patients died from this complication.

In particular, researchers found that these drugs are working well when they are combined with existing treatments

  • One trial using an angiogenesis inhibitor combined with radiation treatment has made a noticeable difference for patients with advanced lung cancer. Patients using this combination did not experience a recurrence of the cancer for 7.4 months on average, compared to 4.3 months for patients who did not use the angiogenesis inhibitor.
  • Another trial combining another angiogenesis inhibitor with chemotherapy achieved a similar result for patients suffering from advanced colon cancer. For the 28 people in the trial, the cancer's growth stopped for an average of 9.5 months, versus 6 months without the new drug.

Researchers emphasize that they have a long way to go, even though the present trials have lasted for years. So far, only 6,500 cancer patients have received the new treatments, according to the Angiogenesis Foundation, which is based in Boston, Massachusetts.


Learn More

  • Tumors depend on blood supply to grow. You can explore what happens when different parts of the body have different needs for blood flow in the Biology Explorer activity, Blood Supply.

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