Summer 2009

Are We Winning the War on Cancer?

Nearly 40 years ago, the nation declared a war on cancer. Today, the pace of research and discovery has us closer than ever to gaining the edge on this dreaded disease.

BY IGNACIO LOBOS

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Dr. Denise Galloway’s office is not easy to find in this large maze of long hallways and many rooms filled with researchers peering into microscopes, glass tubes and petri dishes.

Fred Hutchinson Cancer Research Center has five major research buildings at its South Lake Union campus in Seattle. With nearly 250 full-time faculty, including Galloway, and more than 2,500 others supporting their work, the Center is a busy but calm work space, with people stationed in various labs at all hours of the day and night.

Galloway’s lab is typical of the research floors at the Center, a microcosm, you might say, of the war on cancer. She was a key contributor in international efforts leading to the development of a vaccine for human papillomavirus, the cause of 70 percent of all cervical cancers. At the opposite end on her floor are Dr. Peggy Porter, widely recognized for her contributions to breast-cancer research, and Dr. Brian Reid, who showed that early DNA analysis of esophageal cells in patients with Barrett’s esophagus—a precancerous condition caused by chronic acid reflux—was extremely accurate in predicting cancer risk. It was a key finding, and the test became one of the few proven situations where early detection saves lives.

Like every other floor at the Center, you’ll find some of the cancer research conducted here pinned to the walls, often in the form of colorful explanatory posters that to the uninitiated eye make no sense: codes of DNA, structure of cells, the cold language of chemistry, biology and science at its most complex.

But on a bulletin board near Galloway’s office, a Sunday newspaper cartoon faded by age adds a crisp voice of populism to the clutter of scientific jargon, a reminder of why everyone at the Center is here. It features Lisa Moore, a major character in the Funky Winkerbean comic strip, addressing a Congressional committee; she is bereft of hair and drawn with exhausted eyes by cartoonist Tom Batiuk, himself a cancer survivor.

Lisa is battling breast cancer, and her message is clear: “We can’t give up the fight now,” she says in the strip, “especially when this is a war we can actually win.”

When the war on cancer reaches the funny pages, a raw nerve has been touched in the national consciousness.

The Lisa character died in the strip in October 2007, much to the consternation of thousands of followers. And it happened at a time when many critics were calling the war on cancer lost. A few years earlier, Fortune magazine published a much-cited article, “Why we’re losing the war on cancer (and how to win it).” It was followed in September 2008 by Newsweek’s “We fought cancer … and cancer won.” In April of this year, The New York Times, in its Forty Years’ War series, gave the war on cancer mixed reviews—drawing several hundred reader responses on its Web site.

If there is such a thing as ground zero for this war, now in its fourth decade, surely the Hutchinson Center, the pioneer in bone-marrow transplantation to cure leukemia, is a big part of it. And if this is a war, then Galloway and her Center colleagues are veterans who clearly understand the national thirst for answers.

They chose, after all, to focus their entire careers—for Galloway, 30 years and counting—on one of the most vexing medical problems of our time, an insidious and ugly disease that is expected to kill more than 500,000 Americans and untold millions around the world this year.

“Cancer touches so many people, so many families, including mine,” Galloway said. “So it’s understandable to hear people ask, ‘Why are they not making more progress on cancer? Why are so many people still dying from it?’”

But Galloway wouldn’t be here today, working at her computer with her favorite pooch and lab mascot, Mac, by her side, if cancer had won.

Nor would Dr. Rainer Storb, one of the founders of the Hutchinson Center.

“When I graduated from medical school in 1960, all of the patients with leukemia, all of the patients with lymphomas and myelomas, all the Hodgkin patients, all of them died. Today, most of the Hodgkin’s lymphoma patients can be cured. And children with leukemia, almost all are saved,” he said.

“When we first started doing bone-marrow transplants, we had people in the hospital for months,” said Storb, who has spent part of his career refining a treatment that saved lives but was hard on the body. Today, thanks to Storb and other Center scientists, many patients go home the same day they’re treated after receiving far less toxic treatments.

The techniques developed by many Center researchers over the years have transformed leukemia and related cancers into highly treatable diseases with survival rates as high as 90 percent.

“So when people say we have lost the war on cancer,” he said, “I would say that’s a huge oversimplification of what has happened.”

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A CANCER CRUSADE

When President Richard Nixon signed the National Cancer Act in 1971 and made the “conquest of cancer a national crusade,” Galloway and many of her colleagues at the Center were still undrafted foot soldiers. The Hutchinson Center exists because of funding that came from the cancer act.

“The time has come in America,” Nixon said, “when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease. Let us make a total national commitment to achieve this goal.”

It was easy to get intoxicated by the rhetoric, to get caught up in the excitement. Galloway did. “At the time, I wasn’t sophisticated enough. I didn’t have a full understanding of the complexity of this disease. Now, I would say the cancer act was promising too much.

“In the 1970s, when we started this war, the tools just weren’t there to understand what was going on in the human cell,” she said. “But that has changed with technological advances, with research, and our knowledge has opened up tremendously. We know now that there are many varieties of cancer, many different types of cancer. The complexity just wasn’t appreciated back then.”

“The biology of the more than 100 types of cancers,” according to the National Cancer Institute, the federal agency directing the war on cancer, “has proven far more complex than imagined at that time.”

Galloway came to the Hutchinson Center in 1978, three years after receiving her doctorate in biological sciences. She was part of a two-member team with her husband, the late Dr. Jim McDougall, and both were among many researchers who came to the Center looking to unravel the mysteries of cancer.

Friends tell her that perhaps it’s time to retire, for what is there to do now that the HPV vaccine exists? Lots, it turns out. As many as 100 different human papillomaviruses have been identified, and some of them could even cause other cancers. She has been captivated by polyomaviruses, six of which have been found in people, including children. One of them, Merkel cell polyomavirus, has been identified as the likely cause of the extremely aggressive Merkel cell carcinoma.

Viruses, especially human papillomaviruses, represent the complexity and the ups and downs of the war on cancer. In the 1950s, cervical cancer killed more women in the United States than breast cancer. But the introduction of the Pap smear test—by itself a great example that early detection and prevention work—dropped mortality significantly. Today, with about 11,000 new cases and 3,800 deaths per year, it’s not even listed as one of the most common cancers by the NCI.

And yet, no one really knew for sure what caused cervical cancer until the mid-1980s. The suggestion that a virus might be at play was received with scorn. Finally, it was Dr. Harald zur Hausen who discovered that human papillomaviruses were the culprit. The German scientist won a Nobel Prize last year for his work.

“Just knowing that it was a virus was hugely important. But it took a lot of money, a lot of research, a lot of time and a lot of people to make it happen. And look at the impact.

It has been huge,” said Galloway, adding that zur Hausen’s Nobel validated the work of so many scientists who persevered in their research for a cure.

Today, viruses are known to be responsible for 18 percent to 25 percent of all cancers, something that wasn’t even possible to imagine just a few short years ago.

Despite all these barriers, the HPV vaccine is a major public health success story, a perfect example of basic biomedical research leading to useful technology. But the creation of a new tool also unveiled other complexities in the war on cancer.

Cervical cancer is most prevalent in women in their 40s, but for the vaccine to be effective it should be given to 11- and 12-year-old girls now, and to boys as well before they become sexually active, Galloway said. If that were to happen, cervical cancer could be practically eradicated in just a few decades. But there’s some resistance to the vaccine, approved for females ages 9 to 26, on moral grounds. And there’s the cost.

The three-shot vaccine carries a price tag of $360 in the United States, and it’s not certain yet if it will be covered routinely by medical plans. Just getting health insurance companies to pay for colon-cancer screenings has required legislation in many states, even though if caught early it is highly curable and saves health care dollars in the long run.

The HPV vaccine needs to be affordable outside the United States, where it would do the most good. According to the World Health Organization, cervical cancer remains the second most common cancer in the world, with about 500,000 new cases and 250,000 deaths each year—virtually all linked to HPV. About 80 percent of all cases occur in developing countries, where it remains the most common cancer. Yet, a simple Pap smear responsible for decreasing cervical cancer by 70 percent in developed countries is an enormously difficult task in resource-poor countries.

“So if you ask me how I feel about the war on cancer, I would have to say I feel positive about it. In my area, a lot of progress has been made,” Galloway said. “But I don’t think you’re going to have a eureka moment for all cancers. We’re not going to have one of those aha! moments. And people want that aha! moment.”

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HIGH EXPECTATIONS

“Our recovery plan,” President Barack Obama told the American public earlier this year, “will launch a new effort to conquer a disease that has touched the life of nearly every American, including me, by seeking a cure for cancer in our time.”

It was a bold statement, but it could be understood in the context of a nation hungry for more progress on the war on cancer. A growing number of Americans have been clamoring for that aha! moment

Galloway talked about, even as the United States has been investing less and less in medical research in the past decade. And because of the worldwide recession, private giving also has suffered, pushing many institutions to make painful budget cuts.

“We’ve had to make difficult funding choices,” NCI Director Dr. John Niederhuber acknowledged last December.

The annual budget for the National Institutes of Health, which funds most of the cancer research done in the U.S., has decreased about 7 percent each year for the past several years when adjusted for inflation and has not adequately supported biomedical research. A brain drain from the sciences has been a real concern for many institutions grappling with fewer dollars.

“Young investigators are often the source of the most innovative, creative ideas in science, but we’re losing a generation of young researchers due to chronic underfunding of the NIH,” Hala Moddelmog, president of the Susan G. Komen for the Cure, told a Senate health committee last year.

These challenges have come at a time when the weight of nearly 40 years of research has the nation on the cusp of major medical breakthroughs, according to many cancer experts.

At the Hutchinson Center, for example, researchers are applying what they have learned from leukemia to other cancers and autoimmune diseases. Immunotherapy, which harnesses the body’s own immune system to fight disease, may some day have the same effect on ovarian, breast and prostate cancer that bone-marrow transplantation now has on leukemia.

A majority of Americans believe progress has been made on cancer research, but many are concerned that the government is spending too little money on research, according to a CBS News/The New York Times poll conducted last April.

The poll found that six in 10 Americans believed that at least some progress has been made in finding a cure for cancer, with 30 percent saying “a lot” of progress has been made. The poll also found that 34 percent thought the government was spending too little on cancer compared to other medical research.

Partly because of sinking federal budgets, strong new voices of support for cancer research have risen in recent years, including the Stand Up To Cancer organization, a charitable wing of the Entertainment Industry Foundation that raised $100 million for cancer research last year.

Steve Case, the co-founder of America Online, started the Accelerate Brain Cancer Cure nonprofit with his late brother, Dan, who died of brain cancer in 2002. There’s also Lance Armstrong, the seven-time Tour de France winner who survived cancer and founded an eponymous foundation. In March, he told Congress that he likely would have died had he been diagnosed in 1971 instead of 1996.

Another key player among these new supporters of cancer research is Don Listwin, an electrical engineer by training and Silicon Valley guru who started the Canary Foundation after his mother, Grace, died from ovarian cancer. His goal: “A world of simple tests that identify and isolate cancer at its earliest most curable,” with a blood test in place for solid tumors by 2015.

“That’s what we’re striving for,” said Listwin, who also serves on the Hutchinson Center’s board of trustees. “I’m not a scientist, but I’m an optimist.”

His mother’s death made him think deeply about cancer, and eventually he started to approach the disease from an engineer’s perspective. He sees cancer, and the way we study the disease, as a series of network failures.

A systematic approach that involves researchers from many disciplines and institutions sharing information and working together will give us the edge on the disease, he said.

“We didn’t build the Internet with one person, with one institution. All these people from all these places came together to make it happen,” he said. “We had collaboration across multiple disciplines. Just look at the Human Genome Project. It’s a great example of team science.”

Today, “we have a much better understanding of cancer, but sadly that knowledge has not translated into better survival rates overall,” Listwin said.

And then there’s Matthew Zachary, the founder of I’m Too Young For This! Cancer Foundation. Diagnosed with brain cancer when he was 21, he sums up the frustrations of just about all cancer advocacy groups.

“I’m not that optimistic we’re going to find a magic bullet against cancer, and that’s not something people like to hear. I want to be optimistic, but grounded,” said Zachary, whose foundation focuses on the needs of survivors under age 40.

On the war on cancer, he said, “we open the door to progress but we find a barrier. I never liked the word ‘cure’—with all of its repercussions and expectations.” And yet, “we’re light years away from where we were 15 to 20 years ago. Instead of being a death sentence, cancer is becoming a life sentence, like diabetes.”

What does Zachary want? “We want to reduce late-stage diagnosis of cancer” for people who still have their entire lives ahead of them, he said.

Survival rates for people his age would improve if they were diagnosed much earlier, he said. So educating his peers about early detection is an important goal. He also wants improved access to clinical trials and age-appropriate peer support groups, and he’s counting on a tech-savvy generation to intensify the pressure on government for more funding. And his organization is certainly not about to let up on the scientific and medical community.

The onslaught of pressure from all sectors of society appears to be having some results. Under President Obama’s American Recovery and Reinvestment Act, the NIH received $10.4 billion in new funding in February, with $1.3 billion slated for cancer research in the next two years. Obama also is expected to increase funding for cancer research for fiscal year 2010.

The funds represent a unique opportunity to reinvigorate the war on cancer, NCI director Niederhuber said in an address to the American Association for Cancer Research in April.

“Given that the American Recovery and Reinvestment Act is a once-in-a-lifetime opportunity, we also thought long and hard about what Americans want from all of us,” he said in his speech. “We came back repeatedly in these discussions to the conclusion that they want better ways to prevent cancer, they want the earliest diagnosis, and they want new therapies with fewer side effects that turn cancer into a condition you can live with and not die from.”

Many of these issues are underscored by the pending Kennedy/Hutchison 21st Century Cancer ALERT Act (Access to Lifesaving Early Detection), which could become the most important piece of cancer legislation in 38 years. However, no funding has been allocated for the proposed bill so far.

“Our nation declared the war on cancer in 1971, yet, nearly 38 years later, cancer is expected to become the leading killer of Americans,” Sen. Kay Hutchison of Texas said, when she introduced the bill in March. “We must bring renewed focus and vigor to this fight.”

The power of the bill has been underscored by Sen. Edward Kennedy’s own battle against brain cancer. Kennedy was a key legislator in the 1971 bill.

“The immediate challenge we face is to reduce the barriers that obstruct progress in cancer research and treatment by integrating our current fragmented and piecemeal system of addressing the disease,” Kennedy said. “Last year, my colleague Sen. Hutchison and I agreed that to build on what the nation has accomplished, we must launch a new and more urgent war on cancer.

“We must move from a magic bullet approach to a broad mosaic of care, in which survivorship is also a key part of our approach to cancer,” he said. “By doing so, we can take a giant step toward reducing or even eliminating the burden of cancer in our nation and the world. It’s no longer an impossible dream, but a real possibility for the future.”

The bill addresses many of the concerns expressed by people such as Zachary, Armstrong and Listwin. It’s also a multipronged approach to cancer that many researchers have been espousing for several years.

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THE MACHINERY OF CANCER

Dr. Marc Stewart, medical director of the Seattle Cancer Care Alliance, a partnership of the Hutchinson Center, UW Medicine and Seattle Children’s, likens fighting some cancers to “putting a finger in the dike.”

“Cancer is very tricky. Cancerous cells develop new genetic abnormalities, mutate into new forms and find ways to evade therapies. That’s why progress has been tough with cancer. We’re going to have to continue to make small but very consistent improvements,” Stewart said. “If a drug makes someone survive six weeks longer, that’s not very helpful. It’s a waste of resources and it takes away from the rest of health care.”

The war on cancer, critics argue, has mostly focused on treatments for the latter stages of the disease, with very little funding allocated to early detection. That means most of the research in the last four decades has focused on people diagnosed with late-stage cancer when they have, at best, a 10 percent to 20 percent chance of survival. It’s a cure-driven approach that has helped the U.S. make only modest gains against cancer, critics said.

However, there’s one thing we have definitely learned about cancer: If found at its earliest stage and treated, the survival rate climbs to 90 percent. That’s why so many prominent cancer researchers have been trying to direct more funding toward prevention and early detection research.

Among the leaders is Dr. Lee Hartwell, winner of the 1990 Nobel Prize and president and director of the Hutchinson Center, where prevention and early detection are major activities.

Hartwell has been advocating for a simple blood test that could analyze up to 10,000 different proteins to determine a person’s state of health. Cancer cells produce unique proteins, and the body’s organs produce proteins that signify response to disease—biological markers—and the goal is to come up with a way to identify them.

“The development of sensitive early cancer-detection tests has the potential to save hundreds of thousands of lives each year,” Hartwell said, and do so with another great benefit: Such tests cost a fraction of what it takes to develop and test new drugs for advanced cancer. As health care costs continue to escalate, prevention and early detection could help soften the blow on the nation’s economy.

The Hutchinson Center was one of the institutions chosen by the NCI to look for new cancer biomarkers, and it’s leading collaborations to promote early detection and molecular diagnostics as an international health initiative.

Already, the Center’s scientists are using newly discovered cancer biomarkers to screen women at risk for ovarian cancer. The Center has developed a technique to monitor patients with the precancerous condition known as Barrett’s esophagus, boosting survival rates for esophageal cancer from 5 percent to more than 80 percent. Researchers are focused on improving cancer care, and have developed a highly sensitive test to detect the earliest sign of leukemia relapse; work is ongoing on new tools to predict prognosis and evaluate response to treatment for several types of cancer.

This is the type of research that many cancer advocates such as foundation leader Zachary have no problems supporting.

“The number one reason so many people are dying is because of late detection of cancer,” he said. “I’m not against cancer research for cures, but we need to determine new ways to reduce the risks associated with late detection of cancer.”

The war on cancer has been morphing rapidly, and the new battleground won’t be visible to the naked eye, many cancer experts predict. That’s because cancer will be fought at the nano-level in the years to come.

“The world of cancer care is changing before our eyes,” Dr. Edward Benz, president of Dana-Farber Cancer Institute, told a Senate health committee last year. “The era when treatments were focused on the organ where a cancer originates is coming to end. In the not-too-distant future, patients may receive therapies geared to the specific molecular characteristics of their disease.”

Of course, none of this means scientists should stop looking for cures, even when research suggests that more than two-thirds of all cancer cases could be prevented if the following happens: people stop smoking, exercise regularly and eat a diet rich in vegetables and fruits.

The Hutchinson Center’s Storb doesn’t smoke, and at 74, he is a championship-level rower who eats a healthy diet. And yet, he said, there’s one factor he can’t control. He is growing older.

“Getting older sets the stage for cancer,” he said. “And cures matter. That’s why we have to pay attention to cures.

“Prevention is great but look how well we have done with preventing lung cancer. We know smoking causes cancer and yet, people still smoke,” he said. “Ignoring the end side of things would be a huge mistake. That side will continue to present itself, and the public wants solutions.

“If your daily life was overshadowed by pills, by anxiety that the cancer might return, you would probably want a cure,” he said. “And because we have searched for cures, what has happened, what we have learned, is phenomenal. And some day, that knowledge will really pay off.”

That’s why now, in his fifth decade of his own war on cancer, “I’m still shooting for cures,” he said.


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