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New cancer treatments are coming made to order

http://www.usatoday.com/news/health/2004-06-02-cancer-treatments_x.htm

New cancer treatments are coming made to order
By Liz Szabo, USA TODAY

When Cecily Harris was diagnosed with lung cancer in 1998, the outlook was grim. A tumor near her shoulder grew so big that it broke a rib. Chemotherapy left her too sick to see her grandchildren. She was given nine months to live.

Today, Harris is alive, well and working full time. With her cancer stabilized, her doctor says, the disease has been transformed from a death sentence into a chronic disease.

"I feel as well as a 76-year-old can feel," says Harris, who is from Englewood, N.J. "I'm one of the lucky ones."

Indeed, few cancer patients are as fortunate as Harris. Fewer than 5% of those diagnosed with advanced lung cancer survive five years or more. And only 10% of those taking the same cancer drug, Iressa, see dramatic benefits.

But doctors hope one day to see more patients like Harris.

Experts say her story illustrates the profound changes taking place in cancer research as scientists strive to perfect the new field of personalized cancer treatment. Researchers plan to share the latest news about such "targeted therapies" at the meeting of the American Society of Clinical Oncology beginning today in New Orleans.

"Patient-specific therapy might be the only way we will make inroads into this disease," says Harris' doctor, Roy Herbst, chief of thoracic oncology at M.D. Anderson Cancer Center in Houston. "Every patient's cancer is a little bit different."

The new drugs aren't cures.

But with therapies such as Iressa, researchers are beginning to tailor cancer drugs based on the genetics of a patient's tumor cells. And in a new field called "pharmacogenomics," doctors are developing ways to predict which patients might benefit — and which might suffer serious side effects — from therapies.

It could take five years or so before a wide array of such treatments is available to the average patient, Herbst says. Some might not work out. Yet many experts presenting research at the cancer meeting are optimistic.

By individualizing cancer treatments, doctors say they hope to help patients and avoid some of the grueling side effects of broad-based chemotherapy. Herbst compared Iressa — which Harris began taking in 1999 — to a "laser-guided bomb."

Targeting tumors

Iressa is one of a growing number of drugs which — rather than kill growing cells throughout the body — binds to an enzyme called the epidermal growth factor receptor, or EGFR, and turns it off. The enzyme, which is common in many kinds of cancer, acts as a switch that tells cells to divide and spread without dying.

Recently, researchers discovered one reason why Iressa works so well for some patients, but not for others. Certain tumors have mutated versions of that growth switch, which are particularly vulnerable to Iressa. Doctors are developing tests for the mutation so they can give Iressa to patients who will benefit most, or give the drug earlier.

EGFR also might play a key role in tumors of the breast, colon, ovary, head and neck.

The EGFR enzyme, researchers believe, sets in motion a complicated chain reaction that leads cells to multiply, invade surrounding tissue, develop their own blood supply and spread to organs without dying.

Drugs such as Iressa attack the EGFR molecule on the inside of the cell.

Another drug approved this year, Erbitux, blocks part of the EGFR molecule on the surface of tumor cells.

Doctors say they hope to put together "cocktails" of such drugs, attacking vulnerable links throughout the chain.

'Right drug for the right person'

Scientists might never have expected chronic myeloid leukemia — a cancer of the blood — to have much in common with a rare digestive tract cancer called gastrointestinal stromal tumors, says Harmon Eyre, chief medical officer at the American Cancer Society. As it turns out, however, both diseases respond to a drug called Gleevec, one of the first targeted therapies.

Instead of classifying cancers by organ, doctors are beginning to group them — and develop drugs — based on molecular structures, Eyre says. Because doctors already know so much about EGFR, many new therapies focus on that enzyme, although there are probably dozens of pathways and potential targets.

At the New Orleans conference, doctors plan to reveal the results of combining Tarceva with a drug called Avastin, approved in February, that starves tumors by cutting off their blood supplies.

Doctors note that targeted therapies, like all drugs, have limitations.

Some patients have become resistant to Gleevec, for example. Many promising therapies have not lived up to expectations. And experts note that even with so many new drugs, doctors still don't have enough options for patients.

Doctors say they wish they had more to offer the majority of patients who don't respond to Iressa. "We're just touching the tip of the iceberg," Eyre says.

"The real test will be when we have the right drug for the right person for the right disease."