Celebrating innovation in the lab

Bench-top researchers are on the frontlines of testing new ideas and challenging existing notions of what is possible. Not every experiment works as hoped, but even disappointment and rejection are valuable in helping advance discovery.

“It takes courage and resilience (to do this research),” said Dr. Caroline Alexander, a professor and researcher in the McArdle Laboratory for Cancer Research at UW-Madison.

Seeking to reward and encourage cutting-edge ideas and study, McArdle has launched the Bothwell prize, awarded annually for research papers published by a UW-based team. Instead of a nomination approach, the reviewers consider all such papers published throughout the previous calendar year. Winners are selected based on the potential impact of that work on the understanding or treatment of cancer.

This prize honors the legacy of Claire Bothwell, a young journalist who worked for the BBC in Scotland. She was a staunch advocate for the potential of science to produce transformational ideas for cancer prevention, early intervention and improved treatments.

This year’s inaugural recipients are Dr. Zachary Morris, an associate professor in the Department of Human Oncology, and Dr. Beth Weaver, a professor in the Department of Cell and Regenerative Biology.

Advancing theranostics

Morris is the leader of a team collaborating on a novel precision medicine approach that combines immunotherapy with targeted radionuclide therapy. The latter therapy involves attaching an isotope to a specialized molecule that is selectively taken up by tumor cells following intravenous administration. When labeled with certain isotopes, imaging can be performed to quantitatively map the uptake of the molecule at all tumor sites within a body.

The molecule can also be attached to an isotope that emits therapeutic radiation, which will deliver a low dose of radiation to all tumor sites in the body. The amount of therapeutic radiation administered to a patient can be personalized using information from the quantitative imaging maps.

Combining such targeted radionuclides with a form of immunotherapy called immune checkpoint inhibition successfully eliminated all cancer sites within test mice while leaving healthy tissue unaffected. It has even made “cold” tumors that do not typically respond to immunotherapies more receptive to treatment. The mice given this combination treatment also showed a long-lasting immune response that fights cancer cells injected months later.

Morris and his collaborators are preparing to start clinical trials with recurrent and metastatic cancer patients within the next few years.

“I’m very hopeful and optimistic that this will improve our ability to achieve an effective anti-tumor response in patients by using this combination therapy,” Morris said.

Refining a key cancer drug

Weaver and her colleagues took a closer look at a widely-used chemotherapy called paclitaxel (Taxol). Only about half of breast cancer patients experience a therapeutic benefit from that drug, and doctors have no way to predict whether it will be successful before starting treatment.

By researching how cells multiply across several variations of breast cancer, they found that paclitaxel is more effective in cancers exhibiting high rates of chromosomal instability, where there is uneven chromosome distribution during cell division. Paclitaxel increases this instability to a point that is unsustainable for the cancer cells.

The team found that chromosomal instability can be used to predict the effectiveness of paclitaxel, which could improve treatment plans for a significant number of patients.

“We already know that paclitaxel works for approximately half of breast cancer patients, which is a higher proportion than other treatments. If we can develop a biomarker to identify that half up-front, we can spare all the non-responders the potential toxicities of being treated with this drug.

She added that having a better understanding of how paclitaxel works at a cellular level has provided researchers clues to find ways to overcome drug resistance.