Global Dormancy of Metastases due to Systemic Inhibition of Angiogenesis

Sébastien Benzekry 1, 2, 3, * Alberto Gandolfi 4 Philip Hahnfeldt 2
* Corresponding author
1 MC2 - Modélisation, contrôle et calcul
Inria Bordeaux - Sud-Ouest, UB - Université de Bordeaux, CNRS - Centre National de la Recherche Scientifique : UMR5251
4 Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti"
IASI - Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" [Roma]
Abstract : Autopsy studies of adults dying of non-cancer causes have shown that virtually all of us possess occult, cancerous lesions. This suggests that, for most individuals, cancer will become dormant and not progress, while only in some will it become symptomatic disease. Meanwhile, it was recently shown in animal models that a tumor can produce both stimulators and inhibitors of its own blood supply. To explain the autopsy findings in light of the preclinical research data, we propose a mathematical model of cancer development at the organism scale describing a growing population of metastases, which, together with the primary tumor, can exert a progressively greater level of systemic angiogenesis-inhibitory influence that eventually overcomes local angiogenesis stimulation to suppress the growth of all lesions. We integrate over this increasingly negative global signaling from all sources to track the development of total tumor burden. This in silico study of the dynamics of the tumor/metastasis system identifies ranges of parameter values where mutual angio-inhibitory interactions within a population of tumor lesions could yield global dormancy, i.e., an organism-level homeostatic steady state in total tumor burden. Given that mortality arises most often from metastases rather than growth of the primary, this finding may have important therapeutic implications
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Sébastien Benzekry, Alberto Gandolfi, Philip Hahnfeldt. Global Dormancy of Metastases due to Systemic Inhibition of Angiogenesis. PLoS ONE, Public Library of Science, 2014, 9 (1), pp.e84249. ⟨10.1371/journal.pone.0084249⟩. ⟨hal-00868592v3⟩

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