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A 'Magic Bullet' For Cancer

A "magic bullet" drug that targets a protein active in a wide range of cancers works against not only breast but prostate cancer tumors, researchers said Monday.

The experimental drug, called 2C4, is not designed to cure cancer, but to stop the growth of tumors and give patients a respite. Doctors hope to eventually be able to turn cancer into a chronic but manageable disease with such drugs.

A team at Genentech Inc., which makes 2C4, and Cedars-Sinai Medical Center in Los Angeles, said it works on the same principle as Genentech's Herceptin breast cancer drug, but against a wider array of targets.

"We certainly hope that it will work against a range of solid tumors," Dr. David Agus of Cedars-Sinai, who led the study, said in a telephone interview. "It's pretty cool."

Both 2C4 and Herceptin are monoclonal antibodies -- proteins made in mice and then genetically engineered to home in on a specified target. Cancer researchers have coined the phrase "magic bullet" for such drugs.

In Herceptin's case it is a cell receptor called HER-2/neu, which is overactive in some tumors.

Some breast cancer tumors use HER-2/neu to fuel their growth, and Herceptin blocks it. But some breast tumors do not contain large amounts of HER-2/neu, and they are not helped by Herceptin.

2C4 goes a few steps backward. It, too is a monoclonal antibody, but its target is all the proteins related to HER.

"We found that 2C4 not only targeted HER-2/neu, but that it disrupted cell-signaling among the entire HER family of proteins," Agus, whose team reported its findings in this week's issue of the journal Cancer Cell, said.

"The HER kinase axis appears to be an important growth signaling pathway in most solid tumors," he added. "So if you perturb it, you might expect to see growth inhibition."

And, as hoped, in mice this meant it acted against breast and prostate cancer tumors, Agus's team reported.

They have started tests on 21 patients with a broad range of cancers, including breast, prostate, ovarian and other solid tumors. The Phase I trial is designed to show only that 2C4 is safe but Agus hopes the patients' tumors will also shrink.

Agus said 2C4 works on a similar principle to another promising cancer drug, AstraZeneca's Iressa, a pill that also targets proteins produced only in cancer cells.

Iressa, which is up for Food and Drug Administration consideration next month, targets the epidermal growth factor receptor. Like Herceptin, it is designed to attack only cancer cells so it should not have the toxic side-effects of chemotherapy or radiation therapy, which kill healthy cells along with tumors.

"I think cancer cells are simpler than we think. The same pathways are active in many cancer cells," Agus said.

He believes if any growth signal is blocked in a cancer cell, it will stop growing for a while. "The tumor says 'there is stress here' and stops growing. The patient benefits and it takes two, six, 10 months before the tumor learns to get around the absence of that pathway."

Then another drug must be tried, but in the meantime the patient feels better and, of course, lives longer.

"We have to start to think of cancer as a chronic disease," Agus said. "What we may do is try (something like) Iressa first in many cases because it is an oral drug and this (2C4) is given intravenously."

And he said 2C4 may offer new hope to men with prostate cancer, which kills 30,000 men a year in the United States.

"There's no Herceptin for prostate. There aren't a lot of drugs developed for prostate cancer that work," Agus said.

By Maggie Fox

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