In silico mouse study identifies tumour growth kinetics as biomarkers for the outcome of anti-angiogenic treatment
Year: 2018
Type: article
Abstract: Angiogenesis is a crucial step in tumor progression, as this process allows tumors 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 tumor growth across a wide range of tumors, and no reliable predictive biomarkers have been found to determine the efficacy of anti-angiogenic treatment. Using our previously established computational model of tumor-bearing mice, we sought to determine whether tumor 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 tumor-bearing mouse population. We analyzed tumor growth in untreated mice (control) and mice treated with an anti-angiogenic agent and determined the Kaplan-Meier survival estimates based on simulated tumor volume data. We found that the ratio between two kinetic parameters, k 0 and k 1 , which characterize the tumor’s exponential and linear growth rates, as well as k 1 alone, can be used as prognostic biomarkers of population survival outcome. Our work demonstrates a robust, quantitative approach for identifying tumor growth kinetic parameters as prognostic biomarkers and serves as a template that can be used to identify other biomarkers for anti-angiogenic treatment.
Institutions: University of Southern California, Boston University
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Funder: National Science Foundation
OpenAlex ID: W2949540813