MAKING PROGRESS

From technology improvements to promising treatments, advances are on the way

By Jane E Allen

Finding a reliable screening test remains the Holy Grail of ovarian cancer research, but other goals abound as well. Today's researchers are trying to unravel the underlying biology of the disease, idFrom technology improvements to promising treatments, advances are on the way. identify factors that decrease a woman's risk for ovarian tumors, and detect recurrences earlier with sophisticated imaging technology. Also on the horizon are improved drugs to boost survival. At the same time, patient advocates are expanding their education efforts through a nationwide campaign to publicize the early symptoms of the disease.

LOWERING RISKS
Scientists are identifying factors that can reduce or increase a woman’s risk of developing ovarian cancer. Pregnancy and use of birth control pills have both been associated with lower rates of ovarian cancer, possibly because both suppress ovulation and decrease levels of hormones called gonadotropins. By extension, scientists have suspected that breast-feeding, which further suppresses ovulation and hormones, could also reduce a woman’s risk of ovarian tumors. Kim N. Danforth, Sc.D., M.P.H., and colleagues at Harvard Medical School and the Brigham and Women’s Hospital in Boston recently confirmed that notion by analyzing 16 years of data collected from nearly 150,000 participants in the landmark Nurses’ Health Study and the Nurses’ Health Study II. They found that the longer a woman breast-feeds a baby, the more she reduces her risk, with breast-feeding for extended periods like 18 months over the course of a lifetime most helpful of all.

Diet may influence ovarian cancer development.There’s emerging evidence that diet may influence ovarian cancer development. A Harvard study published in April in the International Journal of Cancer found that eating foods containing kaempferol, one of a group of plant-based antioxidants called flavonoids, may be protective. Researchers reported a 40 percent decrease in the incidence of ovarian cancer among women in the Nurses’ Health Study with the highest intakes of kaempferol - most often consumed in broccoli and tea (not herbal tea) - compared to those women with the lowest intakes. They also found a 34 percent reduction in disease incidence among study subjects whose diets provided the highest amount of luteolin - found in carrots and peppers - compared with those whose diets contained the lowest amounts.

Harvard’s Danforth also conducted a study linking some types of hormone replacement therapy to ovarian cancer. One study suggested that postmenopausal women who take estrogen alone can significantly increase their ovarian cancer risk. Another associated estrogen-progestin use with increased risk as well.

MOLECULAR TARGETS
Experts in the biology of ovarian cancer have long searched for the origins of the disease, with some suspecting that it may begin with the formation of tiny cysts in the covering of the ovary. In a significant development, scientists from the Georgia Institute of Technology and the research-oriented Ovarian Cancer Institute reported in February that ovarian cancer cells seem to form by hijacking a genetic process that normally forms the fallopian tubes. Studying healthy and diseased tissue removed during ovarian cancer operations, they found a protein called PAX8, normally associated with fallopian tube formation, in ovarian cancer cells but not in healthy ovarian tissue. The finding means that PAX8 could be a potential target for diagnostic testing and treatment.

Scientists are searching for the origins of the disease.Meanwhile, researchers worldwide are trying to identify cellular defects that drive the disease, with the idea of designing treatments that correct them. University of Michigan researchers have improved their understanding of cell defects that lead to the second-most-common form of ovarian malignancy, a hard-to-treat type called ovarian endometrioid adenocarcinoma. Researchers at Johns Hopkins Kimmel Cancer Center in Baltimore have found that ovarian tumor cells containing a protein known to spark abnormal cell growth put women at risk of fast, potentially fatal, recurrence. They suggest that testing tumor tissue removed during surgery for this protein, called NAC-1, might identify women at higher risk of accelerated disease.

IMAGING
Detection technology is advancing as well. A combination of positron emission tomography (PET) scans and computed tomography (CT) scans has been proven better at tracking and detecting recurrences than routine CT imaging alone. The findings, presented in June by Australian researchers at the annual meeting of the Society of Nuclear Medicine in Washington, D.C., could help gynecologic oncologists remove more cancerous tissue, initiate chemotherapy earlier and extend symptom-free survival, study authors said.

DRUG TREATMENTS
One of the key obstacles in treating women with recurrent ovarian cancer has been overcoming resistance that can develop during repeated courses of chemotherapy. Preliminary results from an international phase 2 clinical trial of the drug VEGF Trap (aflibercept), reported at the June meeting of the American Society of Clinical Oncology in Chicago, suggest that it holds promise for women whose cancers have stopped responding to chemotherapy. Researchers from Memorial Sloan-Kettering Cancer Center in New York City found that among 162 patients with advanced disease who enrolled in the trial, 85 percent had favorable results after a month of treatment with the drug, which blocks the sprouting of new blood vessels that nourish the cancer and help it spread. Tumors shrank in 8 percent of patients, and the disease was stabilized in 77 percent of them.

In other approaches, scientists continue to compare the effectiveness of the estrogen-blocking drug tamoxifen to that of thalidomide, which blocks blood vessel growth, in treating recurrent epithelial ovarian cancer. Several studies are analyzing the effectiveness of immunotherapy drugs, which send the body’s own immune system on a search-and-destroy mission against cancer cells. Some scientists believe that combining molecularly targeted drugs and hormonal therapies to give a one-two punch may prove the most powerful approach yet.