Quantification of the Synergistic Inhibitory Effects of an Oncolytic Herpes Virus Plus Paclitaxel on Anaplastic Thyroid Cancer Cells

Abstract

Conventional synergy theory explains the inhibitory effects of drug combinations at specific times. Determining the magnitude of inhibition is crucial for exploring the synergy effect. In the results of previous studies, the Chou–Talalay multiple drug effect analysis demonstrated that the combination of a mutant oncolytic herpes virus (G207) and the chemotherapeutic agent (paclitaxel) is the most effective strategy for treating anaplastic thyroid cancer, compared to other combinations such as G207 and NV1023 or paclitaxel and doxorubicin. However, the mechanism behind the synergy effect of G207 and paclitaxel remains unknown, and measuring the synergy effect over time is challenging and expensive. In this study, we formulated a mathematical model to quantify the synergy of G207, paclitaxel, and both over time using the dataset. We conducted a Bayesian estimation of tumor cell proliferation over 16 days using Markov chain Monte Carlo sampling. The Bliss independence was incorporated into the model to compare the observed and expected responses to combination therapy. The expected antitumor effect was significantly lower than the experimental data, suggesting a synergistic effect. Our result showed that the antitumor effect was influenced by the rate of inhibition of tumor growth and the absolute growth delay. Additionally, we found that combination therapy achieved an additional 24% antitumoral effect and a 12-day delay in cell growth. This modeling approach suggests the possibility of quantifying synergistic effects.