Cell-Cycle Synchronization Prior to Radiotherapy: A Mathematical Model of the Use of Gemcitabine on Melanoma Xenografts

Abstract

Radiotherapy can differentially affect the phases of the cell cycle, possibly enhancing suppression of tumor growth, if cells are synchronized in a specific phase. A model is designed to replicate experiments that synchronize cells in the S phase using gemcitabine before radiation at various doses, with the goal of quantifying this effect. The model is used to simulate a clinical trial with a cohort of 100 individuals receiving only radiation and another cohort of 100 individuals receiving radiation after cell synchronization. The simulations offered in this study support the statement that, at suitably high levels of radiation, synchronizing melanoma cells with gemcitabine before treatment substantially reduces the final tumor size. The improvement is statistically significant, and the effect size is noticeable, with the near suppression of growth at 8 Gray and 92% synchronization.

Keywords

• melanoma
• gemcitabine
• mathematical model
• radiotherapy