Molecule by molecule: Researchers dig deep to find cancer's deadly secrets

Author: David Rumbach

SOUTH BEND — Cancer researchers are taking on the dreaded disease one molecule at a time.p. They’re discovering in ever greater detail how cancer cells arise, take root, grow into tumors and — perhaps most crucial of all — spread and become killer diseases.p. Understanding the exact role a particular chemical plays in the progression of cancer gives scientists an edge: They can find another chemical that blocks it and halts the disease.p. But, at the same time, the complex biochemical portrait of cancer emerging now is showing just how varied and formidable the disease really is.p. It’s not one disease, but some say as many as 100 diseases. It has the capacity to mutate, like bacteria, and become resistant to treatment.p. Some observers — voices of skepticism intruding on an otherwise upbeat enterprise — even suggest that the “war on cancer” declared by President Nixon more than three decades ago is actually being lost.p. They argue that some fundamental flaws in the way research is being conducted is stifling true progress.p. Both the reasons for hope, and the enormity of the challenge, were evident at a recent scientific retreat for cancer researchers held at the University of Notre Dame.p. The three-day event brought together researchers from universities where the Indianapolis-based Walther Cancer Institute is currently funding research programs.p. Scientists gave talks or poster presentations on nearly 90 different studies now under way at Notre Dame, Indiana University, Purdue University, the University of Michigan and the University of California, San Diego.p. The researchers are optimistic, naturally, about the state of their chosen field.p. But it has become clear to optimists and pessimists alike that the naive days of searching for a single, miraculous “cure for cancer” are long gone, said Dr. John Durant, Walther Cancer medical director.p. “We’re not going to see ‘the cure’ for cancer,” he said. “This is not a war that will be won easily. It will be won in baby steps.”p. Searching for clues p. Studies presented at the retreat involve virtually all the stages of a tumor’s life cycle, from breakdowns in the body’s system for repairing damaged DNA that lay the groundwork for later malignancies to the biochemical changes in cancer cells that coax them to leave their site of origin and begin their deadly journey to other organs.p. One study at ND, presented by bio-organic chemist Shahriar Mobashery, involves a chemical that might be able to stop metastasis — the process of cancer spread — in its tracks. It is metastasis, Mobashery said, that is especially dangerous.p. “The primary tumor is usually not fatal unless it’s a brain tumor,” he said.p. The promising inhibitor studied at ND — called SB-3CT — has been shown to slow down the spread of lymphoma cells to the liver and prostate cancer cells to bone in specially bred mice.p. So detailed is this study, that Mobashery was actually able to show a computer graphic depicting how the SB-3CT molecule binds with certain chemicals, called gelatinases, that are responsible for metastasis.p. An exciting time p. Mobashery’s colorful dance of atoms, impressive as it was, is not yet a medicine. The ND experiment, like all the others presented at the retreat, are only preliminary steps, and actual treatments based on the work are years away.p. Dr. Rudolph Navari, director of the Walther program at ND, said better treatments are certainly coming, from the work presented during the symposium or from the hundreds of other research projects going on around the country.p. Dr. Rudolph Navari, director of the Walther Cancer Research Center at the University of Notre Dame, talks about promising studies currently under way at ND during a recent scientific retreat for cancer researchers.p. At ND alone, he said, researchers are working with three promising compounds that have proven to kill cancer in mice.p. “We’ve had more new treatments come out in the last five years than in the previous 20,” said Navari, a physician who treats cancer patients in South Bend. “And many more will be coming out in the next five years. It’s an exciting time.”p. The enterprise of cancer research, however, has its critics.p. An influential article in the March 22 edition of Fortune magazine contends that the pace of progress in cancer research is so slow you might conclude the war is actually being lost.p. The article, by Clifton Leaf, points out that the percentage of Americans dying from cancer today is the same as it was in 1970 despite the expenditure of an estimated $200 billion on cancer research in the past three decades.p. By contrast, Leaf writes, the death rates for heart disease and stroke have plummeted by 59 percent and 69 percent, respectively, in the same period.p. Leaf, a cancer survivor, argues that much of today’s cancer research is flawed because it has the goal of shrinking tumors. That seems reasonable, but the fact is that cancer treatments often succeed in eliminating all visible tumors only to have the cancer quickly recur and kill the patient.p. Leaf also faults cancer researchers for their reliance on mice models as the measure of success for their laboratory experiments. Countless treatments that have worked in mice prove useless in people, he points out.p. Jack Dixon, dean of scientific affairs at the University of California, San Diego, doesn’t agree with Leaf’s article, but he took its title as inspiration. Dixon gave his presentation at ND the provocative title “Are We Really Losing the War on Cancer?”p. Dixon has studied two important families of genes called kinases and phosphophatases, which he said act respectively as the “gas” and the “brakes” on cell growth. An excess or shortage of either can lead to cancer. Scientists will learn how to target medicines at those proteins, he said, creating new cancer drugs that are more effective and have fewer side effects.p. Traditional radiation and chemotherapy take a less sophisticated approach.p. “With those, we’re basically trying to kill off your tumor cells before we kill you off,” Dixon said.p. Millions of survivors p. Durant, the Walther medical director, said the pace of progress against cancer may be slower than some people have expected, but it has been meaningful and real nonetheless.p. Durant said that when he began his career in oncology as a research fellow in 1963 in New York City, only one in three people survived cancer. Today, it’s estimated that about 64 percent of people diagnosed with cancer are cured of the disease.p. “That’s taken us from 1963 to 2004,” he said.p. The result is literally millions of people who are alive today because of the medical treatment they received. The National Cancer Institute and Centers for Disease Control and Prevention estimate that the number of cancer survivors increased from 3 million to nearly 10 million in the three decades between 1971 and 2001.p. Success in treatment of children with cancer during the same period is more impressive, Durant said.p. “When you realize that childhood cancer was just terrible, practically all of them died,” he said. “Today, leukemia in children rarely kills them, although we find that some get another malignancy in adulthood.”p. p. More on the Web p. To read about the research efforts of the Walther Cancer Institute, go to .p. To read Clifton Leaf’s article “Why we’re losing the war on cancer (and how to win it),” go to


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