Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.
Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by "normalizing" abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.
Seventh Framework Programme (FP7) under contract No. 278981 “ANGIOPREDICT”. Science Foundation Ireland under grant 13/CDA/2183 “COLOFORETELL”. Science Foundation Ireland under grants 13/IA/1881 and 14/IA/2582. A.T.B. European Commission funded Horizon 2020 Research and Innovation Programme under grant agreement No. 754923 “COLOSSUS”
CommentsThe original article is available at www.nature.com
Published CitationSturrock M, Miller IS, Kang G, Hannis Arba'ie N, O'Farrell AC, Barat A, Marston G, Coletta PL, Byrne AT, Prehn JH. Anti-angiogenic drug scheduling optimisation with application to colorectal cancer. Scientific Reports. 2018;8(1):11182
- Centre for Systems Medicine
- Physiology and Medical Physics