The Long Shot

by Douglas Quenqua Published Winter 2011-12
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Illustrations by Keith Negley“My doctors are trying to poison me.”

These are the words not of a paranoid schizophrenic but of a clear-minded journalist named Leroy Sievers. Five years after being diagnosed with colon cancer, Sievers, increasingly aware that he would not survive the disease, began documenting his experience in a National Public Radio blog called My Cancer. In it, he related his struggles with the disease’s often-debilitating treatment.

“They call the process chemotherapy,” he wrote in 2006, two years before his death. “The idea is to poison the body enough to kill the cancer but not quite kill the patient. Best I can tell, it’s a difficult line to walk.”

Sievers was discovering what cancer researchers have known for decades: that chemotherapy, despite saving millions of lives since it was created in the 1940s, is a blunt, destructive tool. This is because it attacks all rapidly dividing cells in the body. Cancer cells are rapid dividers and highly susceptible to chemotherapy drugs, but so too are hair cells, skin cells, white blood cells, and cells that compose saliva and stomach fluids. The result is a macabre race to treat the cancer before the drugs destroy the patient.

So why are we still using chemotherapy?

Brent Stockwell, an associate professor of biological sciences and chemistry at Columbia, says it’s because researchers have found it extremely difficult to develop drugs that target cancer cells specifically. Although scientists have made dramatic advances in their understanding of cancer’s basic mechanisms during the past few decades, most cancer drugs being used today are forms of chemotherapy developed as far back as the 1980s.

“There are a handful of so-called ‘targeted therapies’ that have been developed for specific types of cancer, including some forms of leukemia as well as skin, prostate, and breast cancers,” says Stockwell. “The survival rates for these cancers today are quite good. But most forms of cancer are still very difficult to treat because we don’t have therapies that are specific to them.”

To understand why, it is helpful to consider how drugs work. Often, a drug is a tiny molecule that slips inside a cell, attaches itself to a harmful protein, and, in doing so, disarms that protein. But the proteins that are responsible for most forms of cancer are slippery and oddly shaped; drugs have trouble attaching to them. For this reason, as Stockwell explains in his new book, The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines, many cancer researchers are reluctant to devote their energies to developing drugs that would target cancer cells directly. Instead, they are trying to fine-tune more traditional chemotherapies with the hope of at least extending cancer patients’ lives and relieving some of the drugs’ devastating side effects.

“Today, if you want to look for drugs to interact directly with those tricky proteins inside cancer cells, you’ll have a hard time getting any funding to do it,” says Stockwell. “Federal funding agencies haven’t invested a lot of money into this type of research lately because it’s considered a lost cause. Even if you scrape up the money to do this sort of work, a scientist needs to consider, Am I going to stake my career on a long shot?”

In his own laboratory, Stockwell is swinging for the fences. He believes he can stop the slippery cancer proteins. At the center of his strategy is a specific protein called Ras, which is known to cause 20 percent of all cancers but which most of his colleagues long ago dismissed as “undruggable.” 

Stockwell concedes that the odds are against him. But to make big discoveries, he says, you need to take big chances.

“To my mind, there are different approaches to science,” he says. “One approach is that you kind of turn the crank, you do what you’re good at, and you move your field forward with incremental advances. My approach is to look for the home runs, to look for the big unsolved questions, and to try to come up with approaches that could really answer those questions and make a huge impact.”

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