Combination of TRAIL-producing oncolytic virus and PAC-1 for treatment of granulosa cell tumours of the ovary

Abstract This study employed mathematical modelling, represented by a system of first-order nonlinear ordinary differential equations, to support the development of cancer therapies for granulosa cell tumours, which lack a suitable mouse model. We investigated the combination of a TNFrelated apoptosis-inducing ligand -producing oncolytic vaccinia virus and the chemotherapeutic agent PAC-1. To analyse the model, we applied singularly perturbed vector field method, which transforms the ODE system into new coordinates, revealing its hierarchical structure and enabling analytical method applications. This approach allowed us to determine equilibrium points of the system and assess their stability. Additionally, the model predicted that while combination therapy alone cannot completely halt tumour growth, it is more effective than monotherapies. Increasing oncolytic virus infection rate could lead to successful treatment within a year. With further data, the model can be refined to facilitate virtual clinical trials, optimising treatment regimens before clinical testing.