Cancer: The War Heats Up

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Scientists have gleaned new insights into the workings of human cells and are chipping away at cancer's deadly grip. Two cancers that often strike children are leukemia and Ewings sarcoma.

For 14-year-old Janet Pendry of Lakeland, Florida, it began when she noticed a simple bump on her shoulder. The teen, who spends her free time hitting the piano, clarinet, and oboe in town bands, didn't think about the bump. It didn't hurt, though it didn't go away. Janet finally went to a doctor who diagnosed it as a cyst, a sac-like lump he believed was nothing to worry about. Other doctors told Janet the same thing, but after a year she decided to have the lump removed. Last February Janet was diagnosed with Ewings sarcoma, a kind of bone cancer found in children and young adults that can spread quickly through the body.

For Corey Wentworth, it started with a fever. The 14-year-old from Calais, Maine, who usually flies on his bike all over town, was suddenly laid low by aching flu-like symptoms in May 1997. His mom took him to a doctor, and later for blood tests at the Eastern Maine Medical Center. Corey remained in the hospital for a month, diagnosed with leukemia, a form of cancer that destroys healthy red blood cells.

Years ago, Corey's and Janet's diagnoses of cancer might have spelled quick death sentences. "When I first heard the news, I panicked," says Corey's mom Brenda Spear. "I thought I was going to lose him." A cure for most cancers still eludes scientists, because cancer isn't a single illness — it's a complex group of diseases marked by the uncontrolled growth and spread of abnormal cells. Normal body cells grow and divide in a precisely controlled way; cancer occurs when cells keep dividing and multiply out of control.

But within the last decade, scientists have gleaned new insights into the workings of human cells. "For the first time, I feel confident we're getting a handle on the biology of cancer," says UCLA researcher Derek Raghavan. As a result, improved treatments have chipped away at cancer's deadly grip.

In fact, a recent barrage of news indicates science may be nearing a major breakthrough in the cancer wars. Researchers will soon begin human testing on a type of drug that has drastically shrunk and even eradicated cancerous tumors (a mass of cells) in mice and left them cancer-free. But clearly the battle is far from over. About 560,000 Americans will die of cancer in 1998.

A LONG DEADLY WAR

The war against cancer has been long and deadly. 4 out of 10 patients now diagnosed with cancer will still be alive in five years. But the majority may not survive that long unless the promising new treatments now slated for testing prove victorious.

Right now, Corey and Janet maintain normal lives. "What bothers me everyday isn't leukemia," says Corey. "It's 14-year-old stuff, like girlfriends who get mad at me." What makes curing cancer so elusive? "Cancer cells are cunning," says Freda Stevenson, a scientist at the University of Southampton in England. The disease-fighting immune system is programmed to destroy abnormal cells, like cancer cells. "But tumor cells have developed ways of switching off the immune system to their presence, thwarting any possible attack," Stevenson says.

Scientists now know normal cells begin to split and produce copies of themselves through a complicated process. Cells produce substances called growth factors. These substances bind to receptors on the surface of cells, like keys fitting into locks. Growth factors trigger cell division.

Cancer cells flaunt the rules. Some have an excess of receptors; some contain their own growth factors; and some possess both. But all cancer cells share one trait in common — they divide uncontrollably. Hundreds of thousands of cancer cells combine to form a tumor. Once the tumor grows big enough, bits of it can break off and spread through the bloodstream to other body parts. There the bits seed, or sprout, new tumors.

Scientists have also begun to zero in on how genes, the cell parts that contain all inherited information, impact human cell division. They know hundreds of genes play different roles in the process.

One gene, for instance, produces a protein called p53 that works like a safety switch. If genetic information goes awry in any human cell, p53 commands the cell to stop dividing until damage is fixed; if the damage is beyond repair, p53 orders the cell to self-destruct. But p53 is often defective itself in people who develop cancer. So the safety switch that should stop damaged cells from dividing is "turned off." Then healthy cells reproduce furiously and turn cancerous. Researchers are trying to find ways to "turn on" defective p53, and halt wildly reproducing normal cells.

What factors trigger cancer cells in the first place? Researchers think most factors are acquired during life-like smoking and unhealthy diets (which together account for two thirds of all cancers!), over-exposure to sunlight, environmental toxins, viruses, and aging itself. But 1 in 20 cases of cancer may be inherited through mutations, defective genetic instructions passed down from parents to children.

STANDARD TREATMENT

Until recently, doctors had few weapons with which to fight cancer: mainly surgery, in which doctors cut out tumors; chemotherapy, one or more potent drugs that stop cancer cells from growing or multiplying; and/or radiation therapy, which bombards cancer cells with high-energy x-rays.

Chemotherapy and radiation have been fine-tuned over the last four decades, but they can still destroy healthy cells as well as cancerous ones. Cancer cells also mutate so fast that they evolve strategies to resist chemotherapy. Side effects of chemo and radiation, such as the depletion of white blood cells and organ damage, are also potentially life threatening.

Corey takes chemo pills every day; once a month he travels to a Bangor clinic for an injection. "I get a little tired afterwards, but don't think about it much," he says. "Most of the time I feel fine." Janet receives monthly chemo shots and periodic intravenous drips (using a thin needle inserted directly in her veins) in the hospital. "I freaked out a little bit at first," she says. "I hated losing my hair," one of chemo's common side effects, along with nausea and vomiting. "But it's just a year of chemotherapy and I'm going to beat it."

ONE SCIENTIST'S WAR

Still in early stages of animal and human testing, the newest arsenal of cancer drugs isnt yet available to Corey or Janet. The most recently hailed advance in drug warfare has shined the spotlight on a scientist looking at cancer cells in a radical way.

For years Dr. Judah Folkman, a surgeon and cell biologist at Boston Children's Hospital, observed that in order to thrive, cancer cells find a way to signal nearby blood vessels to grow and feed. The process is called angiogenesis, the same process the body uses to produce new blood vessels to heal wounds.

Folkman and his colleagues decided to test whether choking off the blood supply to a cancerous tumor could destroy it. At first his experiments provoked ridicule among many colleagues. The traditional approach of cancer research was to seek methods to directly attack the tumor itself. For several years, Folkman tediously experimented with dozens of substances, and found several that did, in fact, partly block new blood vessels from forming in cancerous mice. Some even shrank small mouse tumors. But none of the substances were very effective against large or advanced tumors.

Then in a flash of insight Folkman recalled an earlier observation: extracting one massive cancer tumor from a patient sometimes sparks a number of smaller tumors to sprout suddenly. Folkman formed a new theory: What if a large tumor actually blocks other tumors from growing by competing with them for a blood supply? And what if the substance he was searching for was actually a part of all large cancer tumors?

In other words, Folkman reasoned, a large tumor might secrete a substance that made sure only it was able to form new blood vessels, no other tumors could enlist their own blood supply. If this was true, and if he could discover a similar substance, he might find an answer to choking off the needed blood supply to all cancerous tumors. He could stop cancerous tumors from ever growing in the first place.

After another decade of seemingly endless experiments, Folkman found what he was looking for.

He eventually combined molecular fragments of proteins that he extracted from cancer-ridden mouse urine. The proteins prevented mouse tumors from stimulating blood vessels to feed them. He extracted enough of the proteins from mouse urine to make two drugs that he calls angiostatin and endostatin.

When combined, the two drugs shrink or totally destroy a wide range of tumors in mice. They do so without the side effects of chemotherapy and seem to cure cancer in mice. "I've been waiting for results like these my whole life," says Folkman.

Can enough angiostatin and endostatin be extracted from mouse urine to produce drugs for millions of humans? And will the drugs even succeed on humans? A company called EntreMed is trying to manufacture the drugs, and the National Cancer Institute planned to launch human tests in 1999.

THE WAR'S OTHER FRONTS

As exciting as Folkman's treatment may be, it's only one of 300 new anticancer therapies currently being tested. Another drug is called AG-33-40. Early human tests suggest the drug might not only block angiogenesis, but also metastasis, the spread of cancer tumors to other parts of the body.

Meanwhile, British researchers have started the first human trials of a vaccine for the deadliest form of skin cancer, called melanoma.

The vaccine is made of DNA, or genetic material, from melanoma tumors. The idea is to trigger the immune system to attack the DNA as foreign and destroy it.

In the U.S., researchers are working on a treatment for lung cancer called photodynamic therapy (PDT), which relies on a combination of lasers and lightsensitive drugs. First, the drug is injected into the bloodstream. The drug settles in a cancerous tumor. Then, a laser-emitting tube is snaked into the lungs to the tumor. The laser sparks a chemical reaction in the drug, which inflames the tumor. Then the tumor sheds from the lung's lining, like someone scratching off a scab. PDT will soon be tested to treat intestinal, reproductive, and skin cancers.

Despite these advances, the war against cancer is far from over. But many scientists believe they've reached a turning point in the battle. For teens like Corey and Janet, these advances represent a sign of hope. "I'm going to be a video game designer," Corey says. "I want to be a music teacher," says Janet. Because of the army of new drugs already available and others almost ready for use, their goals may very well come true.