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Advancing ovarian cancer treatment

Gynecologic oncologist Levi Downs Jr., M.D., M.S., says clinical research has led to a much better quality of life for women who have ovarian cancer.

Thanks to research, women are living longer with their disease

Levi Downs Jr., M.D., M.S., knows what most people think when they hear ovarian cancer: imminent death. But, he says, that idea doesn’t reflect current reality.

“It’s true that most women are diagnosed at an advanced stage, and the majority are not going to be cured of their cancer,” says Downs, coleader of the Women’s Cancer Research Program at the Masonic Cancer Center, University of Minnesota. “But there’s a very dramatic statistic I tell people—the difference in average survival from the late 1970s to now.”

Back then, he says, the average survival was around 12 months, and much of that time was spent recovering from surgery and the toxic effects of chemotherapy. Today, the average survival is more than five years—with a much better quality of life.

These changes have occurred as researchers at the Masonic Cancer Center and around the world continuously test new treatment approaches.

“Clinical trials have given us the ability to help people live longer and with a better quality of life,” Downs says. “We’re moving toward women with ovarian cancer being able to manage their disease as a chronic disease.”

Improving, one study at a time

The earliest clinical studies for ovarian cancer established the importance of platinum-based chemotherapy. A major breakthrough in 1996 added the drug paclitaxel (taxol), which increased the average length of survival by 50 percent.

Ten years later, another key study demonstrated the value of intraperitoneal (IP) chemotherapy— in which anticancer drugs are injected directly into the abdomen. Women with ovarian cancer who received a combination of IP and intravenous (IV) chemotherapy lived an average of 16 months longer than women who received IV chemotherapy only.

Today, clinical studies are looking at new ways to treat recurrent ovarian cancer, including immunotherapy, which uses parts of the immune system to fight cancer. Masonic Cancer Center researchers are pioneering a form of immunotherapy using donor immune system cells called natural killer (NK) cells. Melissa Geller, M.D., M.S., and her colleagues published the first-ever study of this treatment for women with recurrent ovarian cancer in 2010. In this initial test of the treatment, researchers learned more about what works and what doesn’t in helping the donor NK cells flourish in the patient’s body. They continue to refine the therapy to decrease its side effects and are currently working on a new clinical trial that’s less toxic.

“This is a whole new avenue of therapy that’s really uncharted,” says Geller. “It could change the way we think about ovarian cancer treatment.”

A research team including Jason Nikas, D.P.T., and Amy Skubitz, Ph.D., recently discovered gene biomarkers that could one day predict which women with advanced ovarian cancer will respond to standard therapy. (Photo: Scott Streble)

On the horizon

Future clinical trials will stem from the basic science research that’s under way now. To take one exciting example, University scientists recently discovered gene biomarkers that may one day predict which women with advanced ovarian cancer will respond to standard chemotherapy. Jason B. Nikas, D.P.T., Amy Skubitz, Ph.D., Walter Low, Ph.D., and Kristin Boylan, Ph.D., examined genetic data derived from ovarian tumor tissue from women with stage III and stage IV cancer. The researchers analyzed more than 20,000 genes to look for patterns that differed between the women who responded to treatment and those who didn’t.

To handle the intensive data crunching the project demanded, Nikas built his own computer and wrote his own software programs. In the end, he found he needed input from just 13 genes to predict whether a woman would do well on the standard treatment.

The finding may change care in two ways. First, women want to know immediately whether the standard chemotherapy will be a waste of their time, being that ovarian cancer is often diagnosed at an advanced stage.

Second, the altered genes may provide a target for drug development. “Taxol only affects one of these 13 genes,” says Nikas. “This research opens the door for designing a cocktail of smart drugs that can modulate most, if not all, of those genes.”

In other studies, Skubitz has identified proteins that might be used one day to detect ovarian cancer in the general population. These biomarkers could also help identify recurrent cancer more reliably than current blood tests, she says.

Benefits for science—and people

To conduct their research, Skubitz and Nikas use small samples of ovarian cancer tissue collected from women undergoing surgery. “Clinical trials are important not only because women who enroll receive the latest treatments, but also so their tissues are stored for research purposes,” Skubitz says.

Their work largely depends on private philanthropy, including grants from the Minnesota Ovarian Cancer Alliance and the Masonic Cancer Center. Most pilot studies and early clinical trials don’t receive government funding, but they’re crucial for discovering the potential new drugs that will then be evaluated in larger trials.

“Words can’t sufficiently express the value of private funding,” Nikas says. “It takes many years to move a project from the lab to the clinic, and if the process is interrupted because government funding runs out, then inevitably all those years of hard work and effort are lost.”

Every woman who is diagnosed with ovarian cancer at a University-affiliated clinic is offered the chance to participate in a clinical trial if she fits a study’s criteria. Not only do these women gain access to promising drugs that aren’t yet available to the general public, but women in clinical trials have better outcomes than those who aren’t.

“Even the patient getting the standard of care on the trial will do better,” Downs says. “We don’t understand why this is.”

What they do understand is that each trial helps to answer important questions about how cancer is diagnosed or treated.

And, says Downs, “Every clinical trial offers us new questions to ask.”

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