Interdisciplinary mathematical modeling and drug delivery research aims to advance treatment of nervous system tumors

MINNEAPOLIS / ST. PAUL (10/27/2023) – University of Minnesota researchers aim to advance the treatment of nervous system tumors through interdisciplinary collaboration that centers mathematical modeling of drug therapy. Collaborators Aaron Li, Mathematics PhD student, and Dr. Kyle B. Williams, Department of Pediatrics postdoctoral fellow, were recently awarded funding for this project from both the Cancer Bioengineering Initiative and the Brain Tumor Program. 

Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas of the peripheral nervous system. The only curative treatment available for these tumors is surgical resection – to date, there are currently no approved targeted therapies for this cancer. All monotherapies have failed to show efficacy against MPNST. These tumors are prone to local recurrence, metastasis, and drug resistance. All in all, MPNSTs present a dangerous and difficult case.

Williams works in the Largaespada Laboratory at the University of Minnesota Medical School. His group has identified several drug combinations that show strong synergy and effectiveness against preclinical MPNST models – some of these combinations can provide complete, durable responses in vivo and are being advanced to early stage clinical trials. To advance this work and the effectiveness of related therapies, Li and Williams plan to work together to drive improvements in mathematical models of the tumor responses to therapy. These models will give the team insight into how to modulate the timing of the drug dosing strategy to help eliminate the emergence of therapy resistance, with the hopes of pushing more – or all – of the tumors into the responder category. 

Li is advised by Prof. Jasmine Foo in the School of Mathematics. Li and Williams will collaborate to develop a stochastic branching process model to predict in vivo behavior from in vitro data. They hypothesize that by integrating the Foo Laboratory’s capability to build predictive mathematical models to optimize drug scheduling and concentrations, the effectiveness of these therapies could be enhanced. The collaboration between Li and Williams will utilize each of their group's strengths, in an iterative manner, to build predictive models of drug responses for the treatment of MPNST and improve treatment outcomes.

“I think there is a lot of value in researching math for its own sake, but being able to connect our work with something tangible that could really make a difference in people's lives in the future makes it even more meaningful,” Li says about his opportunity to collaborate in this hands-on research. “It's really cool to be able to collaborate with Dr. Kyle Williams from the very beginning of this project because it gives us both the chance to better understand each other's fields and shape it in a way that makes sense for both of our work. It's always a challenge to bridge the gap between math modeling and lab and clinical research so I really appreciate that the university is fostering these interdisciplinary collaborations between early career researchers. I think interdisciplinary work in general is very valuable because the areas in between fields are often very underexplored. It's just a matter of having people who are familiar enough with multiple fields to find the right connections. I'm really grateful that my research allows me to learn about other areas.”

Li and Williams were recently awarded $25,000 from the Brain Tumor Program Trainee Brainstorm Pilot Grant and $10,000 from the Cancer Bioengineering Initiative Junior Investigator Pilot Grant to continue advancing this work. The awards will fund experiment materials and Research Assistant funding for both collaborators.