Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy.
The effects of the angiogenic inhibitors endostatin, angiostatin, and TNP-470 on tumor growth dynamics are experimentally and theoretically investigated. On the basis of the data, we pose a quantitative theory for tumor growth under angiogenic stimulator/inhibitor control that is both explanatory and clinically implementable. Our analysis offers a ranking of the relative effectiveness of these inhibitors. Additionally, it reveals the existence of an ultimate limitation to tumor size under angiogenic control, where opposing angiogenic stimuli come into dynamic balance, which can be modulated by antiangiogenic therapy. The competitive influences of angiogenically driven growth and inhibition underlying this framework may have ramifications for tissue size regulation in general.
Hahnfeldt
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P
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Panigrahy
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Folkman
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Hlatky
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D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D043168:Angiostatins; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003094:Collagen / Q000627:therapeutic use; D003510:Cyclohexanes; D043169:Endostatins; D007700:Kinetics; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010446:Peptide Fragments / Q000627:therapeutic use; D010958:Plasminogen / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000627:therapeutic use; D015398:Signal Transduction
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D043169:Endostatins; D010446:Peptide Fragments; D012717:Sesquiterpenes; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol