Dr. Ron Buckanovich: Building a Better Model for Clinical Trial Testing
Solving the riddle of ovarian cancer, one cell at a time
“Cancer always parallels normal biology; it’s just a criminalized version of the system."
The enemy ovarian cancer scientist Dr. Ron Buckanovich stalks is clever. It recognizes barriers that inhibit its growth, and it figures out not only how to overcome them, but how to convert those barriers to work in its favor.
The enemy Dr. Ron Buckanovich stalks is prolific. At least five different versions of it are at play in the human body, each with its own superpower, each with its own kryptonite. What might kill one or two of them won’t be enough to add up to a cure, because its siblings are ready to step in and pick up where the fallen left off.
The enemy Dr. Ron Buckanovich stalks is ruthless. It begins its work deep inside the body where it can avoid early detection, growing noiselessly in an organ that is usually past its productive years, until it has enough of a stranglehold on its host to overcome any weapon that science has been able to throw at it to date. Ovarian cancer’s five-year survival rate is maddeningly low — averaging 47 percent, though that includes all types and stages.
But Buckanovich is committed to changing that. When he arrived at Magee-Womens Research Institute, he made a pledge: “I’m not retiring until we get the drugs that we’re developing into the clinic so I can prove they make a difference,” he said. Today, he adds: “If I never make a penny doing it, it’s fine if I can make a difference … I’ll be able to sleep knowing that I gave it my best shot.”
A cell biologist, Buckanovich approaches the disease at the molecular level, striving to understand what’s different about ovarian cancer cells that makes them so difficult to kill. About 70 percent of women diagnosed with ovarian cancer will experience a recurrence. The analogy he uses is a field of dandelions: if you mow them, they appear to be gone the next day. But within a few weeks, the dandelions return with a vengeance.
That’s because the traditional approach has been to treat the dandelions with a lawnmower, instead of the more painstaking work of killing their roots and destroying their seeds, he notes.
Buckanovich’s lab develops compounds that target stem-like cancer cells, which are common in certain persistent types of cancer, including ovarian. These cells — which comprise about 5 percent of the total ovarian cancer cell population — mimic the body’s healthy stem cells, in that they can create whole systems within the disease.
“Cancer always parallels normal biology; it’s just a criminalized version of the system,” Buckanovich explains. And because the stem-like cells are hard to study and represent such a small sliver of the overall cancer cell population, they have not been a primary therapeutic target.
That’s why a place like Magee-Womens Research Institute is critical, Buckanovich notes: “You need somebody asking that kind of academic question,” he says. “You’ve got to get down to the root of the matter,” because it may be infinitely valuable to the 22,000 women who are newly diagnosed with ovarian cancer each year.
Ovarian cancer survivor Jan Stojanovic knows the value of dedicated research all too well. Diagnosed in 2014 at stage 3c, she underwent surgery and months of chemotherapy, often with her grandson at her side. A little more than a year later, she was in remission, but she knew others who weren’t as fortunate. She is grateful that her cancer was found early and treated at Magee-Women’s Hospital.
“It’s been an amazing journey,” Stojanovic says. “I feel wonderful today. I am on a surveillance plan and still listen to my body. I have some side effects from the treatments, but I am so thankful.”
To date, Buckanovich says they have identified within a given tumor there are at least five different types of cancer cells, each with its own advantages and weaknesses: one is very resistant to chemotherapy; another can resist radiation therapy. One is migratory and helps the cancer to metastasize. They all begin with one stem-like cell population that Buckanovich refers to as “the grandmother:” theoretically, if a drug could kill the grandmother before she has offspring, the cancer could be cured. But if not, other drugs could kill her daughters and granddaughters by targeting their unique vulnerabilities.
Currently, Buckanovich’s lab is testing several drugs in human clinical trials to determine efficacy. The ability to move so quickly from bench to patient was one of the reasons he decided to make Magee-Womens Research Institute his academic home.
Another reason he chose to work at MWRI is the expertise in anti- cancer immunology. He and partners at MWRI have started a new project funded by the Ovarian Cancer Research Alliance. Ovarian tumors create a lot of scar tissue, which scientists theorize is a strategy by the cancer to protect itself from the body’s own immune system. The trials would de-activate the scar tissue to see if immunotherapy could create the same robust results in ovarian cancer that it does in other diseases, such a melanoma. (Immunotherapy is credited with successfully treating former President Jimmy Carter.)
“The immune system can see things we can’t,” and could then be harnessed to help fight the tumor, Buckanovich says. “If we are correct, we can directly move this into clinical trial.”
But the fight against ovarian cancer is unlikely to be a one-and-done endeavor, he warns. A tumor functions like a chronic wound that turns the body’s system against itself, hijacking the immune system to turn it off so the cancer can resist chemotherapy
“It is a little bit of an evil genius,” Buckanovich says, but he is up for the challenge: “[Researchers] haven’t really pushed the needle for ovarian cancer, and so it really motivated me,” he adds. “It’s a population that, really, we need to do a lot more for.”