Dr. Guise: Battling the bone

By Karen Spataro

Mary Beth Gadus had already fought through two rounds of breast cancer when she learned the disease had traveled to her thighbone. In the years that followed, she suffered through radiation therapy, five surgeries and excruciating pain as her femur literally crumbled.

“I had pain every day,” says Gadus, who now relies on an orthopedic implant made of cobalt to replace the bone ravaged by cancer and its treatments. “It was like having a broken leg. I had constant swelling and a severe limp.”

Sadly, her story is not unique. Cancer is a mischievous and persistent enemy that manages to invade other parts of the body, a process called metastasis. Certain tumors are prone to travel to different organs. In the case of breast, prostate and kidney cancers, bones are a favorite destination. Multiple myeloma, a cancer of the plasma cells, also manifests in the skeletal system.

What we don’t know is why. “Why does cancer hide there?” asks Patrick Loehrer Sr., M.D., director of the Indiana University Melvin and Bren Simon Cancer Center. “Why does it flourish in certain places like bone?”

Led by nationally acclaimed endocrinologist Theresa Guise, M.D., a team of newly recruited Indiana University School of Medicine scientists is tackling these very questions with the hope of improving treatments for bone metastases and stopping them altogether.

To understand the team’s research, it’s important to first understand how bones work.

While bones may seem solid and unchanging, they are constantly fixing themselves and regenerating. As part of the body’s normal function, cells called osteoclasts basically chew up old bone. Then the cells build new bone to replace what was lost.

But when cancer spreads to the bone, it hijacks the process. The result can be that osteoblasts kick into overdrive, gobbling up too much and making the bone porous and weak. Or, on the flip side, cancer-impaired osteoclasts can spur abnormal bone growth.

Dr. Guise has dedicated the better part of her career to figuring out how cancer disrupts bone remodeling.

She has identified a specific growth factor, called TGF-beta, that is key to cancer’s success, and she is now working to block the factor from doing its dirty work. But the solution is not simple. TGF-beta can be found elsewhere throughout the body and in some places plays a helpful role, including — ironically — in tumor suppression.

So Dr. Guise and her team are investigating ways to deliver TGF-beta inhibitors directly to the bone in a way that avoids causing damage elsewhere in the body.

“People typically don’t die from bone metastases, but they often die with them,” Dr. Loehrer says. “Bone is not considered a vital organ like the brain or the liver, but it is critical for quality of life.”

Just ask Mary Beth Gadus. Though her cancer is successfully in remission, her thighbone was so damaged that, for years, it limited her ability to perform everyday tasks.

“I’m really high energy. I just wanted to live a normal life. I wanted to work in the yard and play a little golf,” says Mary Beth, a member of the IU Simon Cancer Center Development Board who has helped raise $713,000 for breast cancer research through a grassroots campaign called 100 Voices of Hope. “If Dr. Guise’s research could cause a tumor to be eradicated without damaging the bone around it, then the quality of life for someone with bone metastases would be infinitely better.”

Dr. Guise believes there is no better place to succeed than at the Indiana University School of Medicine. She was recruited here from the University of Virginia in July 2009 and brought with her seven other members of her lab, including an orthopedic surgeon and three scientists with doctoral degrees. She has since added four more members to her team.

Though she looked at some of the top institutions in the country, including Yale, Vanderbilt, Johns Hopkins, Cleveland Clinic and MD Anderson, she ultimately chose the IU School of Medicine because of the opportunity it offered to spend time in both the lab and the clinic and to collaborate with physicians and researchers across a range of disciplines.

Clinically, she treats patients whose bones may have been compromised due to cancer or radiation, chemotherapy, hormones and other therapies. That ties in nicely with another aspect of her research: focusing on the long-term effects of cancer therapies on the bone — an area that’s becoming increasingly important as more patients are cured.

About Theresa Guise, M.D.

A native of Erie, Pa., Theresa Guise wanted to be a veterinarian when she was growing up, “but I was told that was too hard for a girl.”

Dr. Theresa GuiseAfter graduating from high school, Dr. Guise went to work as a lab technician. Bored, she decided to return to college at night to pursue a degree. Medical school never crossed her mind until her boyfriend, who aspired to be a physician, encouraged her to join him and apply. She got in; he didn’t.

Dr. Guise completed medical school and a residency in internal medicine at the University of Pittsburgh. A rotation in endocrinology piqued her interest, and she chose to pursue that field with a fellowship at the University of Texas Health Science Center at San Antonio. Still, she didn’t envision cancer research on her horizon. That changed when she cared for her very first patient in Texas.

“He came into the ER and had a lung mass,” Dr. Guise recalls. “His blood calcium was high. We were consulted to treat that. One day he rolled over in bed and fractured his hip. They found he had metastases to the bone and that is why his hip fractured. My mentor said, ‘This is a great time for you to start your research project.’”

What began as a faculty member’s suggestion over time developed into a career dedicated to understanding how cancer and its treatments affect bones. Despite the frustrations inherent in any research, Dr. Guise has never considered giving up.

“I want to be able to make a difference in patient care,” she says. “My own father got lung cancer and bone metastases. It was almost identical to the first patient I saw in Texas. He died within six weeks of being diagnosed with bone metastases. The treatment was virtually the same as the treatment my patient got 20 years ago. I want to have something else to offer. That’s what keeps me going.”