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Pictures of Health Fall 2006
Cancer: Meeting the Challenge on Many Fronts
Multidisciplinary research efforts produce impressive advances in the prevention, detection and treatment of cancer
By Richard Broderick
Today, no credible researcher would talk of a single, universal “cure” for cancer. Instead, University researchers are tackling the disease as a problem best addressed by multidisciplinary teams ready to look high and low, from the microscopic DNA strands that hide deadly misspellings to the hinterlands of China where non-Western medicines are traditional, in hopes of finding better ways to prevent, detect and treat this daunting illness.
Prevention: Green tea proves protective For University cancer researcher Mimi Yu, the turning point came during a longitudinal research study she and colleagues conducted in China during the late 1980s.
Funded by the NIH, the study followed 18,000 subjects to see what, if any, relationship existed between consumption of green tea and the development of cancers of the digestive tract. “I started out as a nonbeliever,” she admits. “I thought it was insane to think a beverage like tea could have a beneficial effect on such serious diseases.”
What that early study demonstrated, however, was that— far from a worthless nostrum—green tea significantly reduces the incidence of digestive cancers. Further studies in China and the United States have suggested similar preventive benefits for other kinds of cancer. Last year, Yu brought her interest in green tea from the University of Southern California to the University of Minnesota, where she is a new faculty member in the Medical School and the Cancer Center.
She is now putting together an interdisciplinary team to find out exactly how the tea's properties help protect women from breast cancer. An epidemiologist, she was attracted to the University because of its large pool of experts on nutrition and cancer.
An effort drawing on many disciplines
Yu is only one of many University researchers working in interdisciplinary settings to advance the fight against cancer along several fronts—prevention, detection and diagnosis, and treatment.
Some of this work is aimed at improving established practices; other studies are pressing on into heretofore uncharted waters. Some studies are in their earliest stages, while others are on the verge of bringing new medications or protocols to market. Some research efforts— like ongoing investigations of the links between smoking and many kinds of cancer at the University's Transdisciplinary Tobacco Use Research Center—are targeted at the most common forms of disease, while others focus on rare cancers that affect fewer people, but are notable for their virulence and high rates of mortality.
Among studies looking for ways to prevent cancer, work conducted at the University has already helped develop an effective vaccine against cervical cancer, and research studies currently underway are aimed at creating other cervical cancer vaccines as well.
It's long been known that cervical cancer—which kills about 8,000 women in the United States each year, but is the second leading cause of cancer deaths among women worldwide—has a single causal agent: the human papilloma virus. Last year, the FDA approved a vaccine for two forms of the virus known to cause cancer. This year, Levi Downs, a faculty member in the Department of Obstetrics and Gynecology, is leading a multinational study of a vaccine to prevent two other carcinogenic forms of the virus, as well as a trial of a secondgeneration vaccine to follow on the vaccine approved last year. He is also one of the lead investigators for a trial of a therapeutic vaccine—one to treat women with precancerous cervical conditions.
The implications of this work are nothing short of dramatic.
“Cervical cancer is unique not only because it has a single cause, but because it is the first time a vaccine has been shown to prevent the disease,” Downs says. “We have reached the point where it is well within the realm of possibility that cervical cancer will go the way of smallpox.”
Meanwhile, other University researchers are tracking the genetic causes of cancer as a first step toward devising therapies to prevent or cure the disease.
David Largaespada, head of the Cancer Center’s Genetic Mechanics of Cancer Program, led a team that was the first to succeed in using a kind of DNA called Sleeping Beauty (technically known as transposons) to trigger solid tumors in mice. Transposons, also known as jumping genes, insert themselves into and between genes. When these transposons activate a gene that, in turn, sets off a malignancy, it is easier to trace the cancer back to specific cancer genes than with current methods of gene identification.
Right now, the lab mice Largaespada has genetically engineered with Sleeping Beauty are reaching the stage where some of them will develop tumors.
“Genetically, cancer in humans is still poorly understood,” says Largaespada. “The main point of this work is to identify the genes and combinations of genes that cause the diverse types of cancer that are seen in the clinic.”
Detection and diagnosis: Early warning systems
Of all the many unanswered questions about cancer—its causes, prevention and cures—there is one fact that can be stated unequivocally: Early detection of the disease is critically important in determining survival. Catch cancer before it spreads (metastasizes) and a patient's odds go way up.
At the University, cross-disciplinary teams of researchers are hard at work sharpening existing protocols and developing new ones for detecting and diagnosing cancer. One researcher, Timothy Church, a professor in the School of Public Health, is involved in no fewer than three screening trials involving more than 150,000 people designed to refine current screening methods for prostate, lung, colorectal and ovarian cancers. Church also headed the team that established that mailing a kit used for detecting colon cancer directly to homes increases screening rates.
“In Wright County [Minnesota, site of the study], we found you can get a 20 percent increase in screening using this method,” Church says. He is currently seeking funding to expand the study to other localities. Church is also involved in studies investigating the use of vitamin D and calcium in combination to help patients with precancerous intestinal polyps as well as a link between pesticide exposure and prostate cancer among farmers in Wisconsin and Minnesota.
Elsewhere, Michael Garwood and Patrick Bolan, both professors of radiology, have conducted a study of 300 women that combines MRI (magnetic resonance imaging) and MRS (magnetic resonance spectroscopy) into a diagnostic tool for breast cancer.
Garwood and Bolan's work draws upon MRI's ability to detect small lesions, even in women whose breast tissue density makes them poor candidates for mammogram screening, and MRS's ability to detect small amounts of choline, a chemical commonly found in cancer cells. By combining these capabilities, the researchers have come up with a way to provide more accurate diagnoses of breast cancer. And, because individual responses differ to different chemotherapy protocols, the MRI/MRS technique can show changes in tumor size and be used to determine which treatments are working and which are not within 24 hours. This could hasten the development of new drugs by rapidly demonstrating effectiveness.
Now Bolan and Garwood are conducting a study to determine whether their technique, developed at the University's Center for Magnetic Resonance Research, can be replicated on the less powerful equipment normally found in hospital radiology departments.
“If this study goes as we think it will, this technique will become a standard diagnostic protocol,” Bolan predicts.
Treatment: Natural-born killer cells
“In science, you have to be three steps ahead of the game,” observes Jeffrey Miller, a Medical School faculty member and director of the Cancer Center's Bone Marrow Transplant Program.
In his case, Miller is trying to stay three steps ahead of his own groundbreaking 2004 study. It demonstrated that a special protocol designed to stimulate natural killer (NK) cells—a part of the body's immune system— could help some patients with advanced cases of acute myelogenous leukemia (AML) recover enough to become eligible for bone marrow transplants. Miller is now involved in follow-up studies to refine the earlier protocol. The follow-up studies involve a sequence of high-dose chemotherapy, followed by the administration of donor NK cells and interleukin-2 given a short time later to stimulate the NK cells into action. His work has also inspired a new study led by physician Sarah Cooley to see if the NK therapy might work for patients whose breast cancer has spread.
“In this breast cancer study we are following the identical strategy used in our earlier study,” he says. Though the efficacy of bone marrow transplants for treatment of metastatic breast cancer has not been established as clearly as in the case of AML, the disease was chosen for study because, as Miller explains, “it is so widespread and because we have such a highly developed breast cancer program at the U. We just felt that this was a good place to do this.”
Hard work is creating a future with hope
As University researchers push forward the boundaries of cancer knowledge, they increase the reasons for hope. Where once cancer was a disease so feared it was not mentioned above a whisper, today, it is faced head-on with vaccines, medications and treatments that are continually being created and improved.
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