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Ovarian Cancer: A Master of Disguise No More

Ovarian cancer is the fifth leading cause of cancer-deaths among women in the U.S., in large part because a limited understanding of the cancer’s biology and origin has resulted in ineffective prevention and detection strategies. Without much knowledge of how to detect or prevent the deadly disease, the standard of care for women with genetic BRCA mutations that increase their risk of breast and ovarian cancers has been the surgical removal of the ovaries – often around 35 years old. While reducing cancer risk, the procedure also causes early menopause which brings with it increased risks of osteoporosis, depression, and heart disease, and discomforts like hot flashes, hormonal imbalances, insomnia, and a decreased sex drive. What’s more, for these women, removal of the ovaries also means giving up the possibility of getting pregnant. Their choice becomes rolling the dice and risking an often deadly cancer diagnosis, or giving up their youth and life choices.

For care providers, presenting this choice as the only option for risk-reduction was unacceptable and led to seminal studies offering important clues about the cancer’s origin. The results of such studies have refocused efforts of experts in the Penn Ovarian Cancer Research Center (OCRC) and the Basser Center for BRCA, who are developing new detection and prevention strategies for high-risk patients, and at the same time, offering a one-two punch birth control and cancer risk-reduction method for average-risk women who do not have, do not want, or are done having children.

“For a long time we were looking for answers in the ovaries and we weren’t really getting anywhere. It was only when we turned our attention to clues in the Fallopian tubes that we realized they are the answer,” said Ronny Drapkin, MD, PhD, director of the OCRC, who led several of the studies that resulted in the discovery. “We don’t yet know how the cancers occur, but just knowing these tumors start in the tubes and move to the ovaries – and not the other way around – opens up a whole new world of possibilities for prevention and detection. It’s having a tremendous impact on our standard of care for these patients.”

For example, Drapkin says that since the discovery, a number of clinical studies have begun to test whether removal of the Fallopian tubes alone is an effective way of reducing cancer risk. Leaving the ovaries intact and removing only the tubes should spare these patients the early onset menopause, loss of fertility, and all the associated conditions. The mounting evidence showing the effectiveness and benefits of tube-only removal is now making it the standard recommendation for these at-risk premenopausal women.

Just as fallopian tube removal helps preserves fertility for high-risk patients, it also offers a new method of birth control for average-risk women who have already had children.

“Fallopian tube removal is starting to take the place of having the tubes tied, mainly because it’s an equally effective procedure for women who don’t want any more children, and it also reduces the risk of cancer,” Drapkin said. “In fact, for women who are done having children, we’re increasingly recommending the procedure if they are undergoing any type of abdominal surgery. It’s birth control and cancer risk-reduction all in one.”

Though it’s not yet clear how these cancers develop or travel from the Fallopian tubes to the ovaries, the development of new detection strategies is already underway, both in the clinic and laboratory. These latest efforts take advantage of partnerships forged between researchers in the Penn OCRC, the Basser Center for BRCA, the Abramson Cancer Center and the Wistar Institute. While some of the new strategies are more novel, one potential method could take advantage of a standard test already used to detect other gynecologic cancers.

“Like eggs that travel through the fallopian tubes and are discharged through the uterus and cervix, precancerous cells may also be traveling that same path,” Drapkin said. “If that’s the case, it’s possible that standard pap smears, which are not currently used to detect genomic information but are used to detect abnormal cells indicative of cervical cancer, could be an effective way of identifying this ‘debris’.”

At the basic science level, work is being done to develop novel detection systems to determine what cancerous fallopian tubes secrete that normal ones don’t. Through the development of a tumor bank and a rapid autopsy program, researchers will be able to characterize tumors at the time of diagnosis, through treatment and recurrence, tracking the progression of the disease along the way. The hope is that eventually researchers will be able to identify biomarkers that are specifically associated with disease.

“Once we know what we’re looking for, we should be able to track the development of tumors, comparing the presence of these biomarkers before, during and after treatment,” Drapkin said. “The information will not only help us to better understand where the cancers start, but also when it starts, how different treatment methods affect recurrence, and how to intervene earlier.”

Studies going on now are also testing whether microscopic sensors (‘nano-sensors’) deployed in the uterus can detect minute amounts of proteins secreted by very early tumors. The sensors are outfitted with antibodies that can spot these proteins. Once the proteins are identified, the nano-sensor emits a light that can be detected by a sensor similar to an ultrasound machine. Though the system is early in its development, if effective, researchers say eventually these nano-sensors could be deployed in high-risk patients.

“The ultimate goal of these programs is to improve the quality of life for women with ovarian cancer and provide guidance and support to their families,” said Drapkin. “The body of work being done to understand how this disease evolved is unprecedented, and for the first time in years, we’re making significant strides toward understanding it and offering better cancer risk-reduction options for all women.”

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