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

What sparked your interest in individualized medicine?

My interest in individualized medicine was inspired by observing my grandfather go through treatment for esophageal cancer when I was in middle school. He had the opportunity to take part in a clinical trial at University of Chicago, which was able to prolong his life longer than expected. I wanted to be able to contribute to cutting-edge therapy to improve outcomes for patients.

However, the more exposure I had to oncology, I realized that while healthcare professionals very frequently see positive responses to the therapies we give patients, with metastatic disease we almost invariably see the emergence of resistance. Even though we can predict the emergence resistant disease, we have not adapted our treatment strategies to account for this evolutionary phenomenon. Consequently, I want to study more dynamic therapeutic strategies that are informed by the evolutionary dynamics of an individual patient's cancer.

What is your focus as a Gerstner Family Career Development Award recipient?

My focus as a Gerstner Family Career Development Award recipient is on developing and advancing individualized evolutionary therapy strategies, particularly for pancreatic ductal adenocarcinoma (PDAC). This involves using the principles of evolutionary ecology to integrate the dynamics of disease into its treatment. The goal of this approach is to improve clinical outcomes by delaying when a disease starts to become resistant to therapy. This type of research includes comprehensive preclinical studies, theoretical and mathematical modeling, and spatial informatics to understand and influence the eco-evolutionary dynamics of cancer and its microenvironment.

How will your research improve patient care?

Through this work, I aim to improve patient care in several ways:

• Developing individualized therapeutic strategies. By applying principles of Darwinian dynamics to the evolution of resistance during cancer therapy, I seek to develop highly individualized therapeutic strategies that are tailored to the specific dynamics of a patient's disease. This involves delaying or preventing the proliferation of treatment-resistant cells, which may lead to more-effective and longer-lasting treatment outcomes. This approach could fundamentally change the way some cancers are treated, shifting from a one-size-fits-all approach to a more nuanced strategy that considers the individual dynamics of each patient's cancer.
• Incorporating landscape ecology in pathologic analysis. My colleagues and I use machine learning models to precisely map and categorize cell types within the PDAC tumor ecosystem. Spatial biology viewed through the lens of ecological theory can allow us to infer biological significance of spatial relationships between the various "species" of the tumor microenvironment. Cancer cells reprogram and interact with their neighboring cells in a process called niche construction, which gives the cancer cells a fitness advantage and resistance to standard therapies. Our approach aims to improve PDAC treatment by identifying treatment targets to disrupt these niches.
• Reducing treatment toxicity. Evolutionary therapy is designed to lower treatment doses, thus reducing toxicity and improving the patient's quality and length of life. This approach aligns with initiatives such as the U.S. Food and Drug Administration's Project Optimus by optimizing drug dosing to maximize therapeutic effects while minimizing adverse effects. It has the potential to transform patient care in oncology.

How has the Gerstner Family Career Development Award helped advance your research?

The Gerstner Family Career Development Award has been crucial in building the foundation of an independent research program dedicated to studying, developing and advancing the translation of individualized evolutionary therapy strategies that are as dynamic as the disease they treat. The award has provided essential training and preliminary data to demonstrate the feasibility of a multidisciplinary approach to cancer research. This groundwork is pivotal for a successful application for a National Institutes of Health K08 Career Development Award within the next two years.

In addition, the award has facilitated the development of a multidisciplinary mentorship team. My mentors, Martin E. Fernandez-Zapico, M.D.; Robert Gatenby, M.D.; and Carlo Maley, Ph.D., play a crucial role in training in various techniques and disciplines to develop a unique hybrid dry and wet laboratory. Such a laboratory will afford me the opportunity to develop a research program focused on iterative cycles of mathematical modeling and biological experimentation.

Why did you choose Mayo Clinic to explore research?

I chose Mayo Clinic as the venue for exploring this research due to its alignment with my passion for research and its exceptional multidisciplinary, hands-on learning and development opportunities. The project goals mirror Mayo's research priorities. Moreover, the clinic's commitment to providing a supportive environment with a team of mentors with the necessary expertise ensures a successful research outcome. It is a conducive place for innovative cancer research.