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Multiscale modeling of tumor adaption and invasion following anti-angiogenic therapy

Colin G. Cess, View ORCID ProfileStacey D. Finley
doi: https://doi.org/10.1101/2021.08.25.457537
Colin G. Cess
1Department of Biomedical Engineering, University of Southern California, Los Angeles, CA
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Stacey D. Finley
1Department of Biomedical Engineering, University of Southern California, Los Angeles, CA
2Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA
3Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA
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  • ORCID record for Stacey D. Finley
  • For correspondence: sfinley@usc.edu
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ABSTRACT

In order to promote continued growth, a tumor must recruit new blood vessels, a process known as tumor angiogenesis. Many therapies have been tested that aim to inhibit tumor angiogenesis, thus starving the tumor of nutrients and preventing tumor growth. However, many of these therapies have been unsuccessful and can paradoxically further tumor development by leading to increased local tumor invasion and metastasis. In this study, we use agent-based modeling to examine how hypoxic and acidic conditions following anti-angiogenic therapy can influence tumor development. Under these conditions, we find that cancer cells experience a phenotypic shift to a state of higher survival and invasive capability, spreading further away from the tumor into surrounding tissue. Although anti-angiogenic therapy alone promotes tumor cell adaptation and invasiveness, we find that augmenting chemotherapy with anti-angiogenic therapy improves chemotherapeutic response and delays the time it takes for the tumor to regrow. Overall, we use computational modeling to explain the behavior of tumor cells in response to anti-angiogenic treatment in the dynamic tumor microenvironment.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/FinleyLabUSC/Anti-angiogenic-treatment-ABM-model

Copyright 
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 4.0 International license.
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Posted August 26, 2021.
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Multiscale modeling of tumor adaption and invasion following anti-angiogenic therapy
Colin G. Cess, Stacey D. Finley
bioRxiv 2021.08.25.457537; doi: https://doi.org/10.1101/2021.08.25.457537
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Multiscale modeling of tumor adaption and invasion following anti-angiogenic therapy
Colin G. Cess, Stacey D. Finley
bioRxiv 2021.08.25.457537; doi: https://doi.org/10.1101/2021.08.25.457537

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