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A Theoretical Study of Evolutionary Therapy
Neuroblastoma is a paediatric cancer arising from the peripheral sympathetic nervous system. Despite multi-modal therapy, most high-risk cases are expected to relapse. As in the general case of cancer treatment, one reason is the one-size-fits-all treatment protocol. An alternative is evolutionary therapy, which exploits the evolutionary dynamics within a tumour comprising subpopulations with different combinations of mutations.
This project aims to formulate a theory to explain and predict the evolutionary dynamics within a population of cancer cells, driven by multiple drugs and the tumour microenvironment's many components. Although neuroblastoma is my exemplifying system, my interest in evolutionary therapy is a general one. After conceiving the project, I established collaborations with Dr Matishalin Patel (University of Hull) and Dr Sabine Taschner-Mandl (St. Anna Children's Cancer Research Institute).
The most famous example of evolutionary therapy is adaptive therapy, which uses treatment-sensitive cancer cells to suppress their resistant peers. Most if not all of the existing models of adaptive therapy consider two drugs only. However, the rapid COJEC protocol for induction chemotherapy comprises five drugs and certain ALK inhibitors have shown promise in enhancing rapid COJEC. It is necessary to understand how it works with at least six drugs. That neuroblastoma cells have a high level of plasticity further complicates the problem. In January 2024, Francesca Covell became my first PhD candidate (AI and Data Science). She is researching this problem with me and Dr Patel at the University of Hull.
In addition to cancer cells, a tumour contains other components, such as immune cells and importantly for neuroblastoma, Schwann cells. Evolutionary therapy must be planned with these players in mind. In the summer trimester of 2023, Olakunle Yekinni conducted his MSc dissertation research (AI and Data Science) under my supervision at the University of Hull. We used three ordinary differential equations to model the interactions between neuroblastoma and Schwann cells.
