Racing Toward a Cure

Purdue superfan Tyler Trent, whose zest for life and love of the Boilermakers became widely known as he fought the rare bone cancer osteosarcoma, wanted more than anything to motivate people to be advocates and inspire change.

When he died at age 20 on New Year’s Day 2019, he left behind cancer cells that have inspired three research initiatives at the Purdue University Center for Cancer Research for improving therapeutic treatments and changing lives for the world’s youngest cancer patients.

According to the American Cancer Society, osteosarcoma is the most common type of bone cancer in children and teens. About 800 to 900 new cases are diagnosed in the U.S. annually, about half of them in individuals ages 5-20. Trent, who served as the first student member of the Purdue Center for Cancer Research Director’s Advancement Board, was 15 when he was diagnosed with osteosarcoma.

“I want to leave a legacy that motivates people to be advocates. And that can be for whatever they choose, not necessarily cancer,” Trent told an interviewer. “Change only happens when we decide to actually do something about it.”

Trent’s cancer cells are being studied with biodynamic imaging to measure cell motion and response during chemotherapy. The work is being conducted by David Nolte, the Edward M. Purcell Distinguished Professor of Physics and Astronomy, and John Turek, a professor of basic medical sciences in Purdue’s College of Veterinary Medicine.

The researchers are working to understand how Trent’s tissue responds to key cancer drugs. When cells in biopsies or tissue collected during surgery are exposed to chemotherapy agents, effective treatments induce different cell motion than inactive agents. Biodynamic imaging probes 3D tissue using short-coherence dynamic light scattering to measure the intracellular motions inside tissues in their natural microenvironments.

The Purdue team is collaborating with scientists Jamie Renbarger, MD, and Karen Pollok, PhD, from Riley Hospital for Children at Indiana University Health in Indianapolis to identify osteosarcoma chemotherapy sensitivity.

In a groundbreaking development while studying Trent’s donated tumors, the researchers say they discovered a combination therapy that significantly slows tumor growth in models built from his tumor cells. By looking at Trent’s cells, the researchers discovered a variation that is found in tumors that recur. They then tested two different drugs, a Chk1 inhibitor and a bromodomain inhibitor, and found that the two drugs showed promise as a combination therapy.

The second research initiative, also conducted by Nolte and Turek along with Michael Childress, an associate professor of comparative oncology in Purdue’s College of Veterinary Medicine, uses biodynamic imaging to identify chemosensitivity in canine osteosarcoma. The cancer is similar to its human counterpart, so it can be tested with the same chemotherapeutic agents to help find better treatments.

Nolte likens the approach to Doppler light scattering, like a weather radar, to determine how a patient will respond to chemotherapy even before beginning treatment.

“We’re looking at the motion inside living tissue rather than rain droplets, and we’re using infrared light instead of radar. It’s like watching the weather inside living tissue as the tissue is affected by cancer drugs,” says Nolte, who has built a library of data to associate various light patterns with the corresponding response of patients to treatment.

In a related study, the team reported an 84% success rate predicting patient response to therapy in the group’s first complete preclinical trial performed on 19 dogs previously diagnosed with B-cell lymphoma, which is molecularly and clinically similar to lymphoma in humans. They also have tested human patient response to therapy using biodynamic digital holography for ovarian, breast and esophageal cancers, achieving similar accuracies.

“Hundreds of thousands of patients per year are given standard treatments, while only 40% of them actually respond,” Nolte says. “If our method works in human cancers, it means we can help doctors choose better therapies.”

The third Purdue Center for Cancer Research initiative inspired by Trent uses T cells to destroy cancer cells. T cells are a type of leukocyte, or white blood cell, that is an essential part of the immune system. The work to develop this new immunotherapy treatment for cancer is led by Philip Low, the Ralph C. Corley Distinguished Professor of Chemistry and Presidential Scholar for Drug Discovery.

Low and his team developed a technology that allows T cells to be collected from a patient, genetically modified into Chimeric Antigen Receptor (CAR) T cells and injected back into the patient so that their own CAR T cells can target and destroy cancer cells.

Mike Jensen of the Seattle Children’s Research Institute is leading a clinical trial on the technology for the treatment of osteosarcoma.

“We are confident that our researchers will find answers to this disease,” says Tim Ratliff, a distinguished professor of comparative pathobiology in Purdue’s College of Veterinary Medicine and the Robert Wallace Miller Director of the Purdue University Center for Cancer Research. “Tyler’s legacy lives on, and we will not rest until we change the outcomes for patients with osteosarcoma.”