BOSTON (The Boston Globe) -The number of cancer drugs in the pipeline has more than tripled in the past decade, with 402 medications now in human testing across the nation, according to a new survey by the Pharmaceutical Research and Manufacturers of America (PhRMA).

Many represent breakthrough approaches to fighting cancer, ones that promise less toxic, more potent alternatives to conventional radiation and chemotherapy treatments. Researchers say the potential bonanza of new treatments is the long-awaited fruit of the war on cancer launched three decades ago.

For years, it seemed as if the nation was losing the war. Public money was being funneled into basic research. Companies were investing billions more into the development of new drugs. And still, cancer remained the second leading cause of death, after heart disease, claiming 5 million lives every year in the United States.

But today, researchers say, the variety of new approaches and cancer-fighting prospects filling the pipelines of biotechnology and pharmaceutical companies offer hope for radically improved odds in the fight against cancer.

"That doesn't mean a cure is around the corner," said Dr. Lee Nadler, chairman of the department of adult oncology at the Dana-Farber Cancer Institute. "But the expectation is that we're now going to have the army, the navy, the air force and the marines on our side in the fight against cancer."

Today, 19 Massachusetts companies are developing about 35 drugs and testing them in roughly 60 clinical trials against virtually all forms of cancer, including breast, prostate, lung, colon, skin, stomach and pancreatic cancers, as well as solid tumors, lymphomas and leukemias, according to the PhRMA survey.

Among the drugs are vaccines that trigger the immune system to attack cancer cells, monoclonal antibodies that seek out and destroy cancer cells, other antibodies that deliver a toxic payload to cancer cells, and small molecules that set off a reaction in cancer cells known as programmed cell death.

All these therapies are aimed at killing diseased cells without harming healthy cells. Conventional radiation and chemotherapies kill both diseased and healthy cells, causing toxic side effects such as nausea, hair loss and bone marrow damage.

Decades of research, however, improved scientists' understanding of biology. Bit by bit, researchers began to see the biological underpinnings of cancer. By focusing on those processes, drug companies began working on drugs aimed to kill cancer cells without harming normal cells.

Regulatory changes giving priority review to drugs developed for life-threatening diseases with no good available treatments has also helped move drugs more quickly through the pipeline. And drug companies have always been lured to cancer research by the promise of great financial reward.

But progress has been slow and hard won. And researchers caution that much work still lies ahead. It took nearly 20 years for monoclonal antibodies to fulfill their promise as the body's version of guided missiles. And it took just as long for Dr. Judah Folkman's research in anti-angiogenic drugs - those that starve tumors of the blood supply they need to grow - to work its way from the lab into clinical testing.

Today, Mitch Sayare, chief executive of ImmunoGen, a Cambridge, Mass., company that specializes in monoclonal antibody treatments for cancer, said many of the 402 cancer treatments now in development are antibody therapies. In coming years, Sayare said, as drug companies explore their libraries of antibodies, more will enter the pipeline of cancer therapies.

Treatments, such as cancer vaccines, that trigger the body to mount an immune attack on cancer cells have also emerged as a popular area of drug development. Dennis Panicali, president and chief executive of Cambridge's Therion Biologics, said the body doesn't naturally recognize cancer cells as foreign invaders.

At the same time that researchers have learned more about cancer, however, they have also learned more about the immune system. That knowledge, Panicali said, has given scientists tools to manipulate the immune system. Therion is testing 10 different vaccines designed to teach the immune system to recognize cancer cells as foreign invaders and attack them.

"All this innovation is the result of a few decades' worth of basic research," Panicali said. "That research took some twists and turns. Popular opinion pushed research into some dead ends. But eventually we reached a level of understanding that has brought us to this point."

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