In silico mouse study identifies tumour growth kinetics as biomarkers for the outcome of anti-angiogenic treatment

Abstract

Angiogenesis is a crucial step in tumour progression, as this process allows tumours to recruit new blood vessels and obtain oxygen and nutrients to sustain growth. Therefore, inhibiting angiogenesis remains a viable strategy for cancer therapy. However, anti-angiogenic therapy has not proved to be effective in reducing tumour growth across a wide range of tumours, and no reliable predictive biomarkers have been found to determine the efficacy of anti-angiogenic treatment. Using our previously established computational model of tumour-bearing mice, we sought to determine whether tumour growth kinetic parameters could be used to predict the outcome of anti-angiogenic treatment. A model trained with datasets from six in vivo mice studies was used to generate a randomized in silico tumour-bearing mouse population. We analysed tumour growth in untreated mice (control) and mice treated with an anti-angiogenic agent and determined the Kaplan–Meier survival estimates based on simulated tumour volume data. We found that the ratio between two kinetic parameters, k 0 and k 1 , which characterize the tumour's exponential and linear growth rates, as well as k 1 alone, can be used as prognostic biomarkers of the population survival outcome. Our work demonstrates a robust, quantitative approach for identifying tumour growth kinetic parameters as prognostic biomarkers and serves as a template that can be used to identify other biomarkers for anti-angiogenic treatment.