The two keynote speakers at the March 1-2 Molecular Cancer Therapeutics Symposium, sponsored by NCI and the Japan Society for the Promotion of Science, had different topics but similar messages: Cancer researchers must reconsider old assumptions. The symposium was held to celebrate 30 years of cooperation between the United States and Japan in cancer research and included presentations from Japanese and U.S. researchers on a wide range of research related to molecular therapeutics.
Mounds of genomics data on the 110 identified human cancers will be collected and analyzed in the coming years, said Dr. Robert Weinberg, of the Whitehead Institute and Massachusetts Institute of Technology, in his address. "This provokes the question of whether…any fundamental laws [will] be developed that will help us understand all of these various kinds of human cancer," he said. An essential part of developing such laws, he added, is to look more closely at the tumor microenvironment. For example, mounting evidence suggests that stromal cells play an important role in tumor pathogenesis. A number of studies conducted in the United States and Japan have shown how, in mice, stromal fibroblasts interact with cancer cells to significantly accelerate tumor growth and cancer progression. Dr. Weinberg also cited laboratory studies that have pointed to other important elements in the microenvironment, such as specific transcription factors that may help cancer cells acquire attributes that help to promote their proliferation and metastasis.
In terms of future research, such elements, he said, "take the focus away from disrupting autonomous circuits within cancer cells to an additional consideration of how the cancer cells…are recruiting and subverting normal cells [around them] in order to accelerate their own agenda of tumorigenesis."
In her keynote speech, Dr. Julie Buring, of Brigham and Women's Hospital in Boston, discussed some of the controversy surrounding instances where observational studies have appeared to conflict with randomized clinical trials that addressed the same issue. Although such inconsistencies are to be expected, she said, divergent findings can also be a symptom of trials that aren't necessarily attempting to answer the same question.
Observational and randomized trials that looked at the effect of beta-carotene on cancer risk, for example, yielded discrepant findings. The observational studies found a benefit, while randomized trials did not, and in some cases even revealed adverse effects. But the design of the randomized trials, Dr. Buring noted, may very well have been the telling factor. The observational studies, for instance, included people who had a long-term diet high in fruits and vegetables, whereas the randomized trials involved giving high-dose beta-carotene supplements to participants.
The discrepant findings could have meant that the randomized trials were doing what they are supposed to do: confirm or disprove an observational finding. "But maybe [the randomized trial investigators] made the wrong leap," she said. Perhaps the observed benefit in fruits and vegetables came from more than just beta-carotene, she added, and the synergy of the nutrients from the fruits and vegetables was lost.
Looking forward, Dr. Buring said, investigators must thoroughly consider factors like patient characteristics, agent characteristics, and underlying biology up front when designing clinical trials on the basis of observational study results.
The National Institute of Environmental Health Sciences (NIEHS) is rolling out a nationwide research effort to uncover possible environmental and genetic causes of breast cancer. The NIEHS "Sister Study," now running in four states - Arizona, Florida, Missouri, and Rhode Island - is recruiting the sisters of women diagnosed with breast cancer to study shared cancer risks. Recruitment throughout the United States will begin later this year, with an eventual goal of 50,000 volunteers.
NIEHS researchers are enrolling women, aged 35 to 74, who have not had breast cancer themselves but have a sister diagnosed with the disease. During the Sister Study - the only long-term study of its kind - participants will be followed for 10 or more years in hopes of finding why sisters are more likely to develop breast cancer. Scientists speculate that this higher risk could be caused by shared genes, a common diet, a common environment in youth, or even common gene-environment interactions.
There will also be increased efforts to enroll minority women as they, too, are known to be at greater risk for developing breast cancer. For example, African American women aged 30-59 have the highest breast cancer death rate. Dr. Dale Sandler, NIEHS Epidemiology Branch chief and principal study investigator, said, "We hope that a long-term study with many racially and ethnically diverse women will yield new results that will benefit future generations."
For more information about the Sister Study or to enroll, go to http://www.sisterstudy.org or call toll free 1-877-474-7837.
Researchers in New York reported an intriguing finding last week that may offer hope for women who become infertile as a result of cancer treatments like chemotherapy or radiotherapy. In a brief paper published in the March 13 issue of The Lancet, a team from the NewYork-Presbyterian Hospital/Weill Cornell Medical Center reported on a case in which they cryopreserved ovarian tissue from a 30-year-old woman with breast cancer before she underwent chemotherapy. Six years later, after the woman had undergone successful treatment for cancer, the tissue was thawed and transplanted beneath the skin of her abdomen. The patient's ovarian function returned after three months.
Over the next eight months, the team was able to retrieve eight viable oocytes for use in in-vitro fertilization with her husband's sperm. From this, one four-cell embryo was produced and transferred to the patient's uterus. She did not, however, become pregnant. In a news release, the lead investigator, Dr. Kutluk Oktay, said the research "represents a potentially significant reproductive advancement in two respects: first, women can preserve their fertility by freezing their ovarian tissue, and second, pregnancy may be possible even after the tissue remains frozen for a long time."
In an editorial that accompanied the study, Prof. Johan Smitz from the Centre for Reproductive Medicine, University Hospital of the Vrije Universiteit Brussels, Belgium, offered words of caution. Because of many unknowns related to cryopreservation and screening tissue for transplant, he wrote, this option "should still be presented as experimental to patients."