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Multiscale Models of Breast Cancer Progression

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Abstract

Breast cancer initiation, invasion and metastasis span multiple length and time scales. Molecular events at short length scales lead to an initial tumorigenic population, which left unchecked by immune action, acts at increasingly longer length scales until eventually the cancer cells escape from the primary tumor site. This series of events is highly complex, involving multiple cell types interacting with (and shaping) the microenvironment. Multiscale mathematical models have emerged as a powerful tool to quantitatively integrate the convective-diffusion-reaction processes occurring on the systemic scale, with the molecular signaling processes occurring on the cellular and subcellular scales. In this study, we reviewed the current state of the art in cancer modeling across multiple length scales, with an emphasis on the integration of intracellular signal transduction models with pro-tumorigenic chemical and mechanical microenvironmental cues. First, we reviewed the underlying biomolecular origin of breast cancer, with a special emphasis on angiogenesis. Then, we summarized the development of tissue engineering platforms which could provide high-fidelity ex vivo experimental models to identify and validate multiscale simulations. Lastly, we reviewed top-down and bottom-up multiscale strategies that integrate subcellular networks with the microenvironment. We present models of a variety of cancers, in addition to breast cancer specific models. Taken together, we expect as the sophistication of the simulations increase, that multiscale modeling and bottom-up agent-based models in particular will become an increasingly important platform technology for basic scientific discovery, as well as the identification and validation of potentially novel therapeutic targets.

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Acknowledgments

I apologize to the investigators whose work I was unable to discuss in this focused review. This study was supported by Award Number #U54CA143876 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, 244 Olin Hall, Cornell University, 14853, Ithaca, NY, USA

    Anirikh Chakrabarti, Abraham D. Stroock & Jeffrey D. Varner

  2. Department of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA

    Scott Verbridge & Claudia Fischbach

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  1. Anirikh Chakrabarti
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  2. Scott Verbridge
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  3. Abraham D. Stroock
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Correspondence to Jeffrey D. Varner.

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Associate Editor Scott L. Diamond oversaw the review of this article.

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Chakrabarti, A., Verbridge, S., Stroock, A.D. et al. Multiscale Models of Breast Cancer Progression. Ann Biomed Eng 40, 2488–2500 (2012). https://doi.org/10.1007/s10439-012-0655-8

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