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Cancer 'Cure'?

Medically Reviewed by Gary D. Vogin, MD
From the WebMD Archives

May 29, 2001 -- As rule, cancer specialists don't like to use words like "cure" and "miracle," but recent developments in cancer research are changing that. When specialists gathered in San Francisco earlier this month for the world's largest cancer research meeting, more than one speaker used the word "miracle" about Gleevec, the new cancer pill approved for leukemia.

Larry Norton, MD, of Memorial Sloan-Kettering Cancer Center in New York puts it this way: "What we now have is a proof of principle that cancer can be cured with medical treatment." And Norton, who is just taking office as president of the American Society of Clinical Oncologists, says that Gleevec represents just the tip of the iceberg.

John Mendelsohn, MD, president of the University of Texas M.D. Anderson Cancer Center in Houston, told a gathering of medical journalists that "there are about a dozen other compounds in the pipeline" that look just as promising as Gleevec, which made headlines with its record-breaking approval by the FDA.

The FDA approved the drug for a specific type of leukemia called chronic myeloid leukemia, or CML. Just days after the FDA announced its decision, Gleevec was grabbing headlines again by demonstrating efficacy in treating a rare type of stomach cancer called gastrointestinal stromal tumor, or GIST. Before Gleevec, there was no effective medical treatment for GIST.

For several decades, cancer specialists have been chasing a way to attack cancer cells directly without also attacking healthy cells in the body, says Norton. The elusive goal has been to find a single pathway that could penetrate the cancer cell and cause it to "commit cell suicide, a process we call apoptosis," says Norton. But for many years the best researchers believed that "cancer cells were so messed up, that it is impossible to correct the problem through a single pathway," he says.

In the last four years, however, researchers have concentrated on drugs that target certain proteins found in cancer cells. Some of these proteins -- like ones found in patients with CML or GIST -- are enzymes in a family called tyrosine kinases, which stimulate cell growth and production. Gleevec homes in on these enzymes and turns them off. Without the signal to grow, the cancer cells die. Healthy cells are left alone.

Working in laboratories, cancer researchers discovered many of these proteins or receptors in the early 1980s, but it has taken all these years to find a way to attack them, says Mendelsohn. "Now, however, I think the pace will pick up, and we can expect to see one or two of these new compounds developed each year for the next decade," he says.

One to two new drugs developing each year for the next 10 years -- what a thrilling prospect.

"What everybody is excited about is what is in the pipeline," says William J. Gradishar, MD, associate professor of medicine at Northwestern University School of Medicine in Chicago. Gradishar tells WebMD that he doesn't like people to use terms like "miracle" or "cure" when it comes to cancer because he thinks it's deceptive. It "misleads the public and overinflates the reality of where we are and where we hope to be," he says.

But Gradishar says that what is different about cancer research today is that the new molecular knowledge is leading to "more rational drug design that reflects a better and more refined knowledge of the ... disease."

That means, he says, that we can expect to see more drugs that are designed as targeted therapies. The real breakthroughs will come when there is a targeted drug to treat more common cancers like lung cancer or colorectal cancers. "GIST isn't unimportant, but it is relatively rare," Gradishar says. "We have 180,000 new lung cancers diagnosed every year. A target therapy for lung cancer would be really exciting."

And targeted therapies for some of these more common cancers are in the works. Researchers are making headway on a targeted therapy that in early trials is showing good activity in colorectal cancer.

The "weapon" is an experimental, genetically engineered drug called IMC-C225 or cetuximab. It targets a receptor, called epidermal growth factor receptor, on the surface of cancer cells that tells the cells when to grow or multiply. Blocking this receptor weakens the cell, making it more susceptible to chemotherapy, which then kills the cell.

Tumors shrank by at least 50% in 27 people with colorectal cancer who were treated with cetuximab and another chemotherapy drug called irinotecan, or CPT-11. All of these patients had failed standard therapy.

Cetuximab also may prove effective in pancreatic cancer or head and neck cancer. In fact, researchers say any cancer cell that tests positive for the epidermal growth factor receptor is a potential target for cetuximab.

Gradishar says these new molecularly targeted drugs are sorely needed because "we've gone about as far with chemotherapy as we can go. I don't expect to see many new toxic agents [like chemotherapy] being developed. The new goal is to find ways to tweak existing chemotherapy regimens to make them better."

In terms of "tweaking," cancer specialists are optimistic about using old treatments in new ways, says Gradishar. For example, he says that some researchers are reporting better results by manipulating the timing of chemotherapy. For bladder cancer, one new study suggests that chemotherapy first may eliminate the need for surgery to remove the bladder. In another study, researchers demonstrated that when chemotherapy and radiation treatment are given as concomitant therapies, many people with cancer of the larynx can avoid surgery to remove the voicebox.

"These are examples of ways that we are working to find ways for people to be able to live with their disease for an extended period with few side effects. These people can function at a high level, much like people with high blood pressure or diabetes. That's not a cure, but I don't think the goal I described and the goal of a cure are mutually exclusive," says Gradishar.

When physicians gather at medical meetings, they often begin and end their presentations with famous quotes. At this year's gathering of cancer specialists the most oft quoted lines were those of Winston Churchill: "This is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning."

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