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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

View ORCID ProfileSebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt
doi: https://doi.org/10.1101/168823
Sebastien Benzekry
aInria team MONC, Inria Bordeaux Sud-Ouest, Bordeaux, France
bInstitut de Mathématiques de Bordeaux, Bordeaux, France
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  • ORCID record for Sebastien Benzekry
  • For correspondence: sebastien.benzekry@inria.fr
Clare Lamont
cCenter of Cancer Systems Biology, GRI, Tufts University School of Medicine, Boston, MA, USA
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Dominique Barbolosi
dSMARTc Unit, Inserm S_911 CRO2, Aix-Marseille University, Marseille, France
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Lynn Hlatky
cCenter of Cancer Systems Biology, GRI, Tufts University School of Medicine, Boston, MA, USA
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Philip Hahnfeldt
cCenter of Cancer Systems Biology, GRI, Tufts University School of Medicine, Boston, MA, USA
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Abstract

Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0.05). The competition model had to be rejected while the angiogenesis inhibition and proliferation inhibition models were able to describe the data. Additional models including a theory based on distant cytotoxic log-kill effects were unable to fit the data. The proliferation inhibition model was identifiable and minimal (4 parameters), and its descriptive power was validated against the data, including consistency in predictions of single tumor growth when no secondary tumor was present. This theory may also shed new light on single cancer growth insofar as it offers a biologically translatable picture of how local and global action may combine to control local tumor growth, and in particular, the role of tumor-tumor inhibition. This model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 26, 2017.
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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth
Sebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt
bioRxiv 168823; doi: https://doi.org/10.1101/168823
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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth
Sebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt
bioRxiv 168823; doi: https://doi.org/10.1101/168823

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