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Microenvironmental Niches and Sanctuaries: A Route to Acquired Resistance

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Systems Biology of Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 936))

Abstract

A tumor vasculature that is functionally abnormal results in irregular gradients of metabolites and drugs within the tumor tissue. Recently, significant efforts have been committed to experimentally examine how cellular response to anti-cancer treatments varies based on the environment in which the cells are grown. In vitro studies point to specific conditions in which tumor cells can remain dormant and survive the treatment. In vivo results suggest that cells can escape the effects of drug therapy in tissue regions that are poorly penetrated by the drugs. Better understanding how the tumor microenvironments influence the emergence of drug resistance in both primary and metastatic tumors may improve drug development and the design of more effective therapeutic protocols. This chapter presents a hybrid agent-based model of the growth of tumor micrometastases and explores how microenvironmental factors can contribute to the development of acquired resistance in response to a DNA damaging drug. The specific microenvironments of interest in this work are tumor hypoxic niches and tumor normoxic sanctuaries with poor drug penetration. We aim to quantify how spatial constraints of limited drug transport and quiescent cell survival contribute to the development of drug resistant tumors.

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Acknowledgments

This work was initiated during the Woman in Applied Mathematics (WhAM!) Research Collaboration Workshop at the Institute of Mathematics and Its Applications (IMA). KAR was supported in part by the U01 CA202229-01 grant from the National Institute of Health. The Bavarian State Ministry of Education and Culture, Science and Arts joint with the Technical University of Munich provided funding for JPV through the Laura Bassi Award. JPV also wants to thanks the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) for providing a travel grant (CE 243/1-1) to facilitate the initiation of this cooperation.

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Authors and Affiliations

  1. Mathematical Modeling of Biological Systems, Centre for Mathematical Science, Technical University of Munich, Garching, Germany

    Judith Pérez-Velázquez

  2. Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA

    Jana L. Gevertz

  3. Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    Aleksandra Karolak & Katarzyna A. Rejniak

  4. Department of Oncologic Sciences, College of Medicine, University of South Florida, Tampa, FL, USA

    Katarzyna A. Rejniak

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  1. Judith Pérez-Velázquez
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  2. Jana L. Gevertz
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  3. Aleksandra Karolak
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  4. Katarzyna A. Rejniak
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Correspondence to Judith Pérez-Velázquez .

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  1. H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA

    Katarzyna A. Rejniak

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Pérez-Velázquez, J., Gevertz, J.L., Karolak, A., Rejniak, K.A. (2016). Microenvironmental Niches and Sanctuaries: A Route to Acquired Resistance. In: Rejniak, K. (eds) Systems Biology of Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 936. Springer, Cham. https://doi.org/10.1007/978-3-319-42023-3_8

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