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Hypoxia in cancer chemo- and immunotherapy: foe or friend?

Noemi Vitos, Shannon Chen, Shreya Mathur, Ibrahim Chamseddine, View ORCID ProfileKatarzyna A. Rejniak
doi: https://doi.org/10.1101/629907
Noemi Vitos
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa FL 33612;
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Shannon Chen
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa FL 33612;
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Shreya Mathur
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa FL 33612;
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Ibrahim Chamseddine
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa FL 33612;
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Katarzyna A. Rejniak
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa FL 33612;
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  • ORCID record for Katarzyna A. Rejniak
  • For correspondence: Kasia.Rejniak@moffitt.org
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Abstract

Hypoxia, a low level of oxygen in the tissue, is a feature of most solid tumors. It arises due to an imbalance between the oxygen supply from the abnormal vasculature and oxygen demand by the large number of tumor and stromal cells. Hypoxia has been implicated in the development of aggressive tumors and tumor resistance to various therapies. This makes hypoxia a negative marker of patients’ survival. However, recent advances in designing new hypoxia-activated pro-drugs and adoptive T cell therapies provide an opportunity for exploiting hypoxia in order to improve cancer treatment. We used novel mathematical models of micro-pharmacology and computational optimization techniques for determining the most effective treatment protocols that take advantage of heterogeneous and dynamically changing oxygenation in in vivo tumors. These models were applied to design schedules for a combination of three therapeutic compounds in pancreatic cancers and determine the most effective adoptive T cell therapy protocols in melanomas.

Footnotes

  • Research supported by NIH Physical Sciences Oncology Network Grant U01CA202229-04, NIH Physical Sciences Oncology Network Grant U54CA193489-04, and the Moffitt Team Science Award.

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-ND 4.0 International license.
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Posted May 07, 2019.
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Hypoxia in cancer chemo- and immunotherapy: foe or friend?
Noemi Vitos, Shannon Chen, Shreya Mathur, Ibrahim Chamseddine, Katarzyna A. Rejniak
bioRxiv 629907; doi: https://doi.org/10.1101/629907
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Hypoxia in cancer chemo- and immunotherapy: foe or friend?
Noemi Vitos, Shannon Chen, Shreya Mathur, Ibrahim Chamseddine, Katarzyna A. Rejniak
bioRxiv 629907; doi: https://doi.org/10.1101/629907

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