Fighting fat to reduce cancer
Diet and disease
Measure breast-cancer risk in 'pack years'
Improving antibody therapies for lymphoma, leukemia patients
Tracing cancer's family ties
The challenges of HIV superinfection

Fighting fat to reduce cancer

Dr. Anne McTiernan

The National Cancer Institute has chosen the Hutchinson Center to coordinate and participate in a nationwide research effort to better understand the link between obesity and cancer.

The goal of the five-year, federally funded initiative is to avoid an increase in obesity-related cancer deaths in the 21st century similar to the death toll exacted by tobacco in the 20th century. The Hutchinson Center is one of four research centers to receive funding for the Transdisciplinary Research on Energetics and Cancer, or TREC, initiative. The Hutchinson Center also serves as the coordinating hub for the entire effort.

Hutchinson Center researchers are among the world's leaders in understanding the links between obesity and disease. Private gifts from individuals and foundations have funded many early Hutchinson Center studies that have provided the foundation for large, federally funded studies, including the $18 million TREC grant.

Head of the Seattle-based TREC center is Dr. Anne McTiernan, whose research focuses on identifying ways to prevent new or recurrent breast cancer and colorectal cancer with a particular focus on physical activity and exercise.

"We know there's an association between obesity, sedentary behavior and increased risk of certain cancers, such as colon and breast — that's been shown for some time," McTiernan said. "In fact, the American Cancer Society estimates that about 30 percent of cancer deaths are due to poor nutrition, excess weight and lack of exercise. Now we're trying to understand the link between cancer and obesity at a more fundamental, mechanistic level."

The Hutchinson Center's success in conducting studies that aim to understand the interplay of nutrition, physical activity and diet on cancer prevention is one of the key factors that led to its selection as a TREC center, McTiernan said.

"A lot of our researchers are already interested in the association between obesity and cancer. We have a track record in this area," she said. "Another strength that positioned the Hutchinson Center to receive this highly competitive grant is that we have a history of close collaboration between our public-health scientists, who focus on understanding the roles of lifestyle and environment in cancer development, and our basic scientists, who conduct fundamental research to discover the biological mechanisms that underlie the causes of cancer and other diseases."

Diet and disease

Dr. Marc Van Gilst

The diet gurus make it sound easy: Ditch your daily donut and lose five pounds in a month. Yet when it comes to a biological formula for weight loss, there are no predictable calculations, said Dr. Marc Van Gilst, the newest faculty member of the Hutchinson Center's Basic Sciences Division. Gifts from private donors allowed the Center to attract Van Gilst, a highly recruited fundamental scientist from the University of California, San Francisco.

"We're beginning to learn that the body's metabolic pathways aren't fixed — they're flexible," Van Gilst said. "They can be rearranged in response to conditions that our bodies are unfamiliar with, such as changes in diet or physical activity, which make it hard to predict how the body will respond."

The ability of one's metabolism to manage dietary intake is essential for healthy development and longevity, he said, and glitches in the system can lead to serious diseases like diabetes and cancer.

As a way to untangle the vast web of metabolic pathways that respond to diet, Van Gilst's research focuses on molecules that are likely to be the lynchpins of the system: a family of proteins that sense nutrients and relay signals to stimulate or dampen the activity of enzymes that digest, store or detoxify what we eat. These proteins may also be potential drug targets for diseases like diabetes, obesity, cancer or other conditions in which metabolism has gone awry.

The interplay of diet and human diseases, particularly cancer, is a major focus at the Hutchinson Center, and Van Gilst's leading-edge research will be key in helping unlock life-threatening mysteries.

Measure breast-cancer risk in 'pack years'

Older women who have smoked for 11 or more "pack years" — the lifetime equivalent of a pack a day for at least 11 years — face a 30 percent to 40 percent increased risk of developing breast cancer as compared to women who've never smoked, according to a new Hutchinson Center study.

What's more, the researchers found that long-term smokers who add combination hormone-replacement therapy (estrogen plus progestin) to the mix increase their odds of getting breast cancer by 110 percent — more than double that of women who've never smoked or taken HRT.

These findings, by Drs. Christopher Li, Janet Daling and Kathi Malone, were based on a study of women 65 to 79.

An interesting and encouraging finding was that once a woman stops smoking, within about 10 years of quitting her risk of breast cancer falls back to that of someone who never smoked. This suggests that recency of smoking may be particularly important with respect to breast-cancer risk, Li said.

Improving antibody therapies for lymphoma, leukemia patients

The age-old challenge faced by every cancer researcher is one of simple precision: how to selectively target and kill cancerous cells, while causing the minimal amount of collateral damage to healthy cells, the innocent bystanders in this cellular battle.

Several years ago, scientists at the Hutchinson Center helped to pioneer one elegant approach to the problem. In radioimmunotherapy, antibodies, a natural component of the immune system with the ability to recognize and attack cancer cells, are loaded with radioactive molecules. The antibody transports the source of radiation to the tumor sites, where the targeted cells are confronted with a molecular one-two punch: Antibody binding initiates the process of cell death, while the radioactive atom delivers deadly radiation to the cancerous cells.

The pioneering work of Drs. Fred Appelbaum and Oliver Press, among others, established the Center as an international leader in this field. As it evolves, the next generation of medical researchers, including Dr. John Pagel, step up to the task of making radiolabel therapy safer and more effective for leukemia and lymphoma patients.

Recently awarded a faculty position at the Hutchinson Center, Pagel began his research career at the Center under Press' supervision.

"John joined my laboratory in 2000 and since that time has impressed everyone in our group with his tremendous energy, determination, unparalleled industry, superlative laboratory skills, intelligence and his dedicated approach to translational research," Press said.

The Center recruited Pagel and established his new lab with the support of private gifts. Pagel now leads the leukemia studies of radioimmunotherapy at the Center as the principal investigator of several human clinical trials.

Tracing cancer's family ties

Dr. Debra Friedman

As a pediatric oncologist, Dr. Debra Friedman often has the unfortunate job of telling parents their child has cancer. Inevitably, the shocked parents have two questions: Why did my child get cancer? Will my other children get cancer? Friedman's next unfortunate job is to answer, "I don't know" to both, and to explain that these are active areas of research.

A recent study Friedman led is beginning to shed some light on the second question. Friedman found that the siblings of long-term childhood cancer survivors have an increased risk of cancer overall. For several cancer types, she found that siblings also have increased risk of developing the same cancer. For siblings of children with cancers such as leukemia, Hodgkin's disease, Wilms tumor, neuroblastoma and bone tumors, the risk of getting the same cancer was 1.5 times greater than the general population. The risk for siblings also was elevated if their brother or sister had developed a second cancer.

Although the findings may seem alarming, childhood cancers are relatively rare, Friedman said. And like many such studies, there are more questions raised than answered. More research needs to be done to better understand the genetic contribution to childhood cancer, she said.

"What this study tells us is that we need to do more work to better define some of these patterns of cancer among family members," she said. "That could then lead to molecular studies where we can look for genes that are involved in these cancers and then be able to provide these families with targeted genetic counseling with respect to their risk."

The challenges of HIV superinfection

When it comes to HIV infection, lightning really can strike twice. A recent Hutchinson Center study has found that having HIV and getting reinfected with a different strain of the virus — once thought a rare occurrence — may actually be quite common. These findings have major implications for the development of an AIDS vaccine.

Bhavna Chohan and colleagues in Dr. Julie Overbaugh's lab have found that reinfection may occur almost as often as first infections in women with continued exposure to HIV-1. In the first long-term study of the incidence and timing of HIV-1 reinfection in individuals infected through heterosexual contact — the population most typical of the global HIV pandemic — Chohan found the risk of reinfection was about half the predicted risk of initial infection.

The possibility of reinfection indicates that an immune response triggered by a vaccine to prevent infection by one strain of HIV may not protect against all other strains. A vaccine's effectiveness is likely to vary in different populations unless a method is developed which guards against many virus strains.

"It's critical to better understand the immune responses that are lacking in people who become reinfected so that improving these responses can be the focus of vaccine-development efforts," Chohan said.

A parallel study by scientists at the University of California, San Diego, found similar HIV reinfection rates in high-risk men who have sex with men.