Cancer cell structure offers new targets for treatment

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Discovery of cancer cell structure offers new targets for treatment

By Daniel Q. Haney, Associated Press, 3/26/2001 15:24

NEW ORLEANS (AP) Scientists have figured out the precise three-dimensional structure of a spot where cancer cells receive growth instructions, a discovery that may speed the development of exquisitely precise new treatments.

One of the forces that makes cancer grow rampantly is a substance called insulin-like growth factor, or IGF. Without this hormone, many cancers will shut down and die.

Researchers have long understood the importance of IGF but so far have been unable to exploit this knowledge to make new cancer drugs.

The obvious strategy is to block the spot that lets IGF get into cells. However, this structure, called a receptor, is extremely similar to another one that serves as the entry point for insulin.

Although normal cells can survive without IGF, they still need insulin. The difficulty is making a drug that gums up the IGF receptor but not the lookalike insulin receptor.

On Monday, researchers from Amgen Inc. announced they have deciphered the 3-D crystal structure of the IGF receptor. This means they know exactly what it looks like down to the last atom.

Scientists already know the structure of the insulin receptor. So now they can compare the two and look for parts that are unique to the IGF receptor.

Dr. Xiaotian Zhu described the discovery at a meeting in New Orleans of the American Association for Cancer Research.

The goal is to craft molecules that will cover up part of this receptor, destroying its ability to take in chemical signals, without also disabling the insulin receptor.

''We found quite a few structures that are unique to IGF,'' Zhu said. ''This could not have been predicted otherwise. We think this will greatly accelerate the drug discovery process.''

Dr. Edward Sausville of the National Cancer Institute noted that many types of cancer, especially prostate tumors, are fueled by IGF. Blocking it might be combined with standard chemotherapy as a cancer treatment. The approach might also be used on patients with precancerous prostate abnormalities to keep them from turning into cancer.

Development is still early, however, and it is unclear whether IGF blockers being developed by Amgen will actually work this way.

Sausville said the goal of this and other research is to develop drugs that are ''precisely designed to address abnormalities present in each individual's tumor.''

Such drugs might work with far fewer side effects than standard chemotherapy, which broadly attacks all rapidly growing cells in the body.

Zhu said blocking IGF should be safe, since people who have naturally occurring IGF deficiencies are unusually small but otherwise healthy.

One thing that makes cancer different from normal tissue is that it refuses to die. Experiments suggest that cancer cells need IGF to escape the usual limits on the number of times a cell can divide. When IGF is shut off, cancer cells often simply stop growing and expire.

Among other reports at the meeting Monday:

Dr. Robert Kreitman of the cancer institute combined an antibody with a poison made by pseudomonas bacteria. The treatment zeros in on cancerous blood cells that have unusually large numbers of a protein called CD22 on their surface. The treatment is showing promise in otherwise untreatable cases of hairy cell leukemia and chronic lymphocytic leukemia.

Dr. Brian Ross of the University of Michigan said a scan called diffusion-weighed magnetic resonance imaging may be able to tell within a few days whether chemotherapy is working against tumors. The scan reveals whether water in the tumors is moving more freely, as happens when cells die. Testing is under way on 12 patients.

Dr. Sergio Huerta of the UCLA Center for Human Nutrition found preliminary evidence that a synthetic form of vitamin D might protect against colon cancer. Ordinary vitamin D produces dangerously high calcium levels if taken in large quantities. In mice, at least, the synthetic vitamin reduced the risk of colon cancer with only a modest calcium rise.

-- Anonymous, March 26, 2001

Answers

Fascinating article, Brooks.

-- Anonymous, March 28, 2001

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