Ahead of the Curve on Head and Neck Cancers

Dr. Dwight Perry’s voice is an important part of his work as a minister and theological education leader. So when his wife noticed he sounded a little too raspy in December 2005, Perry went to his doctor. Follow ups with a specialist at UW Carbone Cancer Center confirmed he had stage one laryngeal cancer.

“It was a shock to me,” he said. “I don’t drink. I don’t smoke. I lead a fairly healthy lifestyle.”

Following multiple surgeries and eventual radiation treatment, Perry is cancer free and feels he received the best possible care from UW Carbone. Even after moving to Chicago, he still commutes to Madison for annual visits with his oncologists, Drs. Seth Dailey and Paul Harari.

“The care and treatment at the Carbone Center are excellent,” Perry said.

UW Carbone’s expertise in head and neck cancer treatment and research are held in high esteem nationally, as evidenced by the National Cancer Institute awarding UW a Specialized Program of Research Excellence (SPORE) grant in 2016. UW’s Head and Neck SPORE was the first such grant given to a Wisconsin institution, and their accomplishments led NCI to renew their SPORE funding and designation for another 5 years.

In this next phase, SPORE leaders have defined several projects that include improving immunotherapy responses and identifying new biomarkers that can predict treatment effectiveness before a patient starts that therapy.

Innovating treatments

While immunotherapy has been a significant break-through treatment for many patients, they are not effective for many others. Researchers are working to understand more of the barriers that make tumors unresponsive in order to overcome them.

Harari, who serves as Director of the Wisconsin HN SPORE, is partnering with Drs. Zach Morris and Jamey Weichert on an effort that combines immunotherapy with targeted radionuclide therapy. Using a molecule developed by Weichert, researchers can directly target cancer cells for both imaging and therapeutic purposes.

In mouse models, this molecule can be used to deliver an individually-calculated low radiation dose directly to cancer cells. Combined with immunotherapy, the treatments eliminated the cancer cells while leaving surrounding healthy tissue unaffected. This method of radiation has also helped make even “cold” tumors responsive to treatment.

“It’s a highly personalized treatment,” Morris said of the radiation dosimetry involved.

The study mice have also shown a lasting immune response to their cancer. Project leaders hope to initiate phase 1 clinical trials for patients with metastatic and recurrent cancer in the next few years.

Another immunotherapy-related project involves researching how a specific family of molecules, called TAM receptors, work together to trick a patient’s immune system into believing cancer cells are normal tissue, and if this effect can be reversed through a combination of immune checkpoint inhibitors and radiation.

“We know that these molecules keep the tumor cold, but if we hit those molecules and flip the switch, can we make you sensitive to these already-available immunotherapies?” said Dr. Deric Wheeler, who is co-leading the project with Dr. Justine Yang Bruce.

This project also includes plans for a clinical trial to evaluate that combination therapy.

Refining treatment

Harari is also working with Drs. Dave Beebe and Sheena Kerr on efforts to identify biomarkers that can predict how a patient would respond to various treatments.

Currently, clinicians can’t predict how effective a certain course of treatment will be for a patient until after that regimen has started. This project is intended to optimize treatment plans and save patients unnecessary side effects of treatments less likely to work.

“In terms of survivorship, getting the best treatment first is obviously what’s best for the patient, rather than possibly going for a therapy that doesn’t help them, and then they have to try another therapy,” said Kerr.

Researchers will evaluate which biomarkers are linked to existing patients’ treatment effectiveness through use of single cell RNA sequencing of tumor cells, tissue microarrays that contain tumor tissue from multiple patients, and circulating tumor DNA that is captured and filtered by a microfluidic device Beebe developed.

This project also includes a clinical pilot study that would create artificial tumor microenvironments using cells isolated from patient tumor tissue. Having these patient-specific environments, researchers can compare how treatments perform on the devices and how consistent that is with the real-time treatments of those patients.

Beebe is hopeful this engineered environment will prove a better lab testing model than using animals and become the future standard practice.

A key driver for SPORE researchers’ success has been access to large variety of head and neck cancer patient tissues.

Through new outreach efforts, including an informational video, SPORE collaborators were able to increase consent levels from about 10 percent when the SPORE first began in 2016, to more than 90 percent now.

Harari notes that all of these elements contribute directly to the ultimate mission of the SPORE, which is to advance research and treatment success for patients with head and neck cancer.