Even before she learned to multiply and divide, Nara Yoon, PhD, assistant professor of mathematics and computer science, was flexing her mathematical skills by playing Omok (five-in-a-row), Chinese chess and 15 puzzles.
Games that were inherently mathematical just came naturally to her.
In school, she developed what she calls a profound interest in mathematics, which led her to choose it as one of her majors in college and in her graduate studies, undertaken at Ewha Womans University in South Korea, and then for her PhD, which she earned in applied mathematics at Case Western Reserve University in Ohio.
Dr. Yoon鈥檚 first move after earning her doctorate is telling about her philosophy on the higher purpose of math: She took a position as a mathematician in the Jacob Scott Laboratory at the Cleveland Clinic, which uses mathematical and experimental models to develop an understanding of how resistance to cancer therapies develops, with the goal of increasing the efficacy of targeted therapies and radiation.
鈥淭o me, mathematics transcends mere numbers and textbook logic; it is an integral part of our world,鈥� Dr. Yoon said. 鈥淎t Case Western, I was exposed to numerous professors engaged in diverse mathematical applications. Among these, the health-related field intrigued me the most, given its close connection to our everyday lives.鈥�
Dr. Yoon鈥檚 most recent exploration of how math can be an instrumental element of healthcare is 鈥�,鈥� published in 2023 in Physics in Medicine & Biology and co-authored with colleagues from the Cleveland Clinic and Case Western Reserve University.
Unlocking Secrets of the Bystander Effect
Radiotherapy eliminates cancer cells through targeted radiation exposure. Though it is one of the most widely used cancer treatments, some aspects of it are not completely understood due to its physical, chemical and biological complexity鈥攊n particular the 鈥渂ystander effect,鈥� whereby cells affected by irradiation convey beneficial effects to other cells not directly targeted for irradiation. Dr. Yoon says this phenomenon is thought to be linked to enhanced immunity after cancer and radiation exposure.
Dr. Yoon and her research team decided to study this effect by developing a mathematical model that explores the population dynamics of viable tumor cells, T cell lymphocytes (cells that protect the body from infection and may help fight cancer), immune triggering cells (cells with an anti-tumor response), and doomed cells (damaged cells doomed to die), and elucidates their interactions with one another. Her contributions to the study include analyzing the established model, focusing on prognosis patterns, treatment possibilities and promising treatment plans.
鈥淭he model allows for the simulation of two scenarios: an easily activated immune system responding to cancer, limiting tumor size even without radiation鈥攊mmune limited鈥攁nd a suppressed immune system lacking sufficient power to combat the cancer鈥攊mmune escape,鈥� Dr. Yoon said. 鈥淯nlike the 鈥榠mmune-limited鈥� scenario, effectively treating 鈥榠mmune-escape鈥� cancer requires a sophisticated radiation strategy.鈥�
These understandings are particularly important in treatment of cancer that is initiated when a tumor鈥檚 size is in a curable range. 鈥淲hen treatment begins at an opportune time, careful consideration is needed for designing radiation, such as Spatially Fractionated Radiotherapy (SFRT),鈥� Dr. Yoon explained. 鈥淭his aims to maximize the bystander effect, while minimizing the radiation amount, thereby reducing damage to immune cells compared to cancer cells.鈥�
The model demonstrated that the highly varied dose distribution in SFRT can make a drastic difference in tumor-cell killing compared to the uniform radiation dose distribution, not only enhancing but also moderating the killing of cells depending on immune response triggered by various factors. In other words, SFRT can be customized to more precisely treat tumors based on the immune characteristics of the cells near it.
Implications for Cancer Care
鈥淚n the course of our research, we uncovered valuable insights into the impact of immune response on cancer prognosis through analysis based on our newly developed tumor model,鈥� Dr. Yoon said. 鈥淚n identifying the two distinct modes of tumor status鈥攊mmune limited and immune escape鈥攚e were able to further delve into promising approaches for treating cancer.鈥� Using patient-specific data and a data-based parameter estimation method, she said this study can be applied in the clinic for the design of individualized treatment plans.
Their research also offers that 鈥渦nderstanding the role and response of the immune system during and after radiotherapy is of critical importance as we move further into the era of immunotherapy.鈥� In developing mathematical models that intend to explain phenomena occurring during cancer treatment, we gain a deeper understanding of complexities at the cellular level鈥攚hich is vital to developing clinical studies and identifying new treatments.