• Research

    2023 Gerstner Awardee’s ‘evolutionary therapy’ targets pancreatic cancer treatment resistance

This illustration shows a cancerous growth (red) in the pancreas (yellow).

Ryan Carr, M.D., Ph.D., a medical oncologist in Mayo Clinic's Department of Oncology, is a recipient of the 2023 Gerstner Family Career Development Award. The competitive awards are presented annually by Mayo Clinic Center for Individualized Medicine to researchers conducting innovative investigations to predict, prevent, treat and cure diseases using individualized medicine approaches.

Dr. Carr is working to develop an individualized treatment approach for pancreatic cancer that applies the principles of evolution to potentially prevent or delay the ability of pancreatic cancer to develop treatment resistance.

Ryan Carr, M.D., Ph.D.

"Resistance to cancer drugs is the primary cause of death in patients with pancreatic cancer, and really with any kind of 'incurable' cancer," Dr. Carr says. "We're working to figure out how to prevent that resistance from emerging."

Dr. Carr's "evolutionary therapy" strategy aims to maintain some sensitive cancer cells to out-compete and suppress other cancer cells that have evolved to become resistant to treatment. It also focuses on treating pancreatic cancer in a more dynamic way in response to the patient's individual disease behavior.

"For example, if the tumor shrinks too much, we back off and stop the chemotherapy to allow sensitive cells to regrow. And then, at the next treatment time, we would administer a lower dose," he says. "This could help maintain long-term disease control with resistance less likely to emerge."

Pancreatic cancer occurs in the pancreas, which is an organ in the abdomen that plays a vital role in producing digestive enzymes and hormones to control blood sugar levels. More than 60,000 people in the U.S. were diagnosed with pancreatic cancer in 2022, and nearly 50,000 died of the disease.

Over the course of the two-year study, Dr. Carr and his team will use advanced techniques, including machine learning algorithms, immunophenotyping tools for analyzing diverse immune cells, and spatial transcriptomics to study messenger RNA activity to evaluate different treatment strategies. They'll take an in-depth look at the cancer cells in each tumor as well as the complex ecosystem of blood vessels, molecules and other cells surrounding each tumor, known as the tumor microenvironment.

"Our goal is to predict how those interactions are related to treatment resistance and the survival of the patient and which of those interactions are most important," Dr. Carr says.

Ultimately, Dr. Carr and his team hope the study will lay a foundation for a new treatment strategy that targets the pancreatic cancer ecosystem and not just the cancer cells.

"Pancreatic cancer is one of the deadliest malignancies, and we've made little to no progress over the course of decades of research," Dr. Carr says. "I feel we need a completely new perspective, and I'm hopeful this study will result in meaningful changes."

The Gerstner Family Career Development Awards are benefactor-sponsored initiatives that promote a specialized workforce for individualized medicine discovery, translation and application. Made possible by a grant from the Louis V. Gerstner, Jr. Fund at Vanguard Charitable, the awards provide important seed money for early-stage investigators interested in launching a career in individualized medicine.

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