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The end of chemo? One magic pill may hold answer

From Tuesday's Globe and Mail

In a coffee shop, on the second floor of a Loblaws superstore in the west end of Ottawa, Zavie Miller and three friends are laughing as the sunlight falls on their faces.

They discuss travel plans and children, the usual stuff, but there is giddiness in their voices, a sense of wonder at the ordinary events in their lives.

They all have chronic myelogenous leukemia (CML), a slow-moving but deadly form of cancer. They keep it in check, however, by popping a pill or two a day.

No chemotherapy with its debilitating side effects for them. Just a drug called Gleevec.

"I take one pill a day. It is really unbelievable," says Mr. Miller, 68.

"I have virtually no side effects."

He volunteers at a soup kitchen and the National Gallery, and recently took a trip to New York with one of his daughters.

Some of his friends have side effects, but nothing like the severe vomiting, depressed immune systems, hair loss, mouth sores and other miseries caused by conventional chemotherapy. Most cancer drugs carpet bomb the body, damaging healthy cells as well as cancerous ones. Gleevec is a smart bomb, designed to kill only cancer. It has turned their leukemia into a chronic disease.

The end of chemotherapy? If that sounds too utopian, picture Mr. Miller and his friends, enjoying their coffee and their extraordinary good luck. They are the future, at least as it is envisioned by scientists convinced there must be a better way to treat cancer.

There are some side effects: Tracey Feldman, 36, for example, is a little self-conscious about her pale skin.

"We all turn white, like ghosts," she says, and shows the group her alabaster stomach. They all start to laugh, and lift their shirts to compare bellies.

Mr. Miller wants them to inspect his scalp. Other patients have reported that Gleevec restored colour to their grey hair, and he bends his head over the table, pointing to a few strands of black mixed in with the white.

They grew after he started the treatment, he insists.

Yet it's fun to listen to their happy chatter, and easy to see why Gleevec is an inspiration for scientists around the world working on drugs that will kill cancer cells but leave healthy tissue alone. Some of those researchers predict that the next 10 years will see dramatic changes in the way cancer is treated, that the next 20 or 30 years could see the end of conventional chemotherapy for most patients.

To kill cancer, doctors often come close to killing their patients.

"Many treatments put people near death," says Philip Branton, scientific director of the Institute of Cancer Research, part of the Canadian Institutes of Health Research.

That's because conventional chemotherapy drugs are essentially poisons. Nitrogen mustard, the first modern chemo drug, is a derivative of the mustard gas used during the First World War.

It destroyed the lymphatic tissue and bone marrow of its victims, and this made medical researchers think something similar might kill fast-growing cancer cells.

By 1942, two researchers at Yale, Louis Goodman and Alfred Gilman, were ready to try nitrogen mustard in a human patient. A 48-year-old silversmith volunteered. He was in the terminal stages of lymphatic cancer, but after 10 doses, his tumours disappeared.

The scientists were on to something, and nitrogen mustard became the first of many toxic compounds found to be effective against cancer. Chemotherapy became an important tool for doctors, in addition to surgery and radiation, and is used to treat many forms of the disease.

Childhood leukemia, testicular cancer and Hodgkin's disease are now regularly cured with combinations of chemotherapy drugs. But patients endure enormous suffering to rid their bodies of cancerous cells.

"We recognize it is obviously not the way to do it, not with what we now know," Dr. Branton says.

What we now know -- thanks to the genetic revolution -- is much more about what makes cancer cells different from healthy ones. They contain damaged or mutated genes. These genes produce aberrant proteins that can cause cells to go haywire, reproduce at a rapid rate and refuse to die.

The molecular approach to treating cancer involves identifying these mutated genes, finding the proteins they produce, then coming up with drugs to stop those proteins from working.

It may sound relatively straightforward. But the gene involved in CML was one of the first cancer genes to be identified in the 1970s, Dr. Branton says. It took more than two decades for researchers to figure out what it does and find something capable of stopping it.

The CML mutation occurs when two chromosomes swap chunks of genetic material. A bit of one gene, from chromosome No. 9, gets added to another gene on chromosome 22. The result is a cancer gene that produces an abnormal protein not found in healthy cells.

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