Global dormancy of metastases due to systemic inhibition of angiogenesis.

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 i...

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Autores principales:	Sébastien Benzekry, Alberto Gandolfi, Philip Hahnfeldt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95ce1086d84a431c9d4fe3d293e5d0a6
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spelling	oai:doaj.org-article:95ce1086d84a431c9d4fe3d293e5d0a62021-11-18T08:37:09ZGlobal dormancy of metastases due to systemic inhibition of angiogenesis.1932-620310.1371/journal.pone.0084249https://doaj.org/article/95ce1086d84a431c9d4fe3d293e5d0a62014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465399/?tool=EBIhttps://doaj.org/toc/1932-6203Autopsy 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. As a departure from modeling efforts to date, we look not just at signaling from and effects on the primary tumor, but 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 metastatic disease rather than growth of the primary per se, this finding may have important therapeutic implications.Sébastien BenzekryAlberto GandolfiPhilip HahnfeldtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84249 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sébastien Benzekry Alberto Gandolfi Philip Hahnfeldt Global dormancy of metastases due to systemic inhibition of angiogenesis.
description	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. As a departure from modeling efforts to date, we look not just at signaling from and effects on the primary tumor, but 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 metastatic disease rather than growth of the primary per se, this finding may have important therapeutic implications.
format	article
author	Sébastien Benzekry Alberto Gandolfi Philip Hahnfeldt
author_facet	Sébastien Benzekry Alberto Gandolfi Philip Hahnfeldt
author_sort	Sébastien Benzekry
title	Global dormancy of metastases due to systemic inhibition of angiogenesis.
title_short	Global dormancy of metastases due to systemic inhibition of angiogenesis.
title_full	Global dormancy of metastases due to systemic inhibition of angiogenesis.
title_fullStr	Global dormancy of metastases due to systemic inhibition of angiogenesis.
title_full_unstemmed	Global dormancy of metastases due to systemic inhibition of angiogenesis.
title_sort	global dormancy of metastases due to systemic inhibition of angiogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/95ce1086d84a431c9d4fe3d293e5d0a6
work_keys_str_mv	AT sebastienbenzekry globaldormancyofmetastasesduetosystemicinhibitionofangiogenesis AT albertogandolfi globaldormancyofmetastasesduetosystemicinhibitionofangiogenesis AT philiphahnfeldt globaldormancyofmetastasesduetosystemicinhibitionofangiogenesis
_version_	1718421575212990464

Global dormancy of metastases due to systemic inhibition of angiogenesis.

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