Experimental and Computational Analyses Reveal Dynamics of Tumor Vessel Cooption and Optimal Treatment strategies
Publication Date
2-2019
Description
Cooption of the host vasculature is a strategy that some cancers use to sustain tumor progression without—or before—angiogenesis or in response to antiangiogenic therapy. Facilitated by certain growth factors, cooption can mediate tumor infiltration and confer resistance to antiangiogenic drugs. Unfortunately, this mode of tumor progression is difficult to target because the underlying mechanisms are not fully understood. Here, we analyzed the dynamics of vessel cooption during tumor progression and in response to antiangiogenic treatment in gliomas and brain metastases. We followed tumor evolution during escape from antiangiogenic treatment as cancer cells coopted, and apparently mechanically compressed, host vessels. To gain deeper understanding, we developed a mathematical model, which incorporated compression of coopted vessels, resulting in hypoxia and formation of new vessels by angiogenesis. Even if antiangiogenic therapy can block such secondary angiogenesis, the tumor can sustain itself by coopting existing vessels. Hence, tumor progression can only be stopped by combination therapies that judiciously block both angiogenesis and cooption. Furthermore, the model suggests that sequential blockade is likely to be more beneficial than simultaneous blockade.
Journal
Proceedings of the National Academy of Sciences
Volume
116
Issue
7
First Page
2662
Last Page
2671
Department
Biomedical Engineering
DOI
https://doi.org/10.1073/pnas.1818322116
Recommended Citation
Voutouri, Chrysolavantis; Kirkpatrick, Nathaniel D.; Chung, Euiheon; Mpekris, Fotios; Baish, James W.; Munn, Lance L.; Fukumura, Dai; Stylianopoulos, Triantafyllos; and Jain, Rakesh K.. "Experimental and Computational Analyses Reveal Dynamics of Tumor Vessel Cooption and Optimal Treatment strategies." Proceedings of the National Academy of Sciences (2019) : 2662-2671.