Physical targeting of therapy-resistant tumor cells

We are utilizing advanced models of the tumor microenvironment to study quantitative cellular responses to the dynamics of therapeutic electric field exposure. We focus on detailed responses mediated by the altered physical properties of tumor tissues that are challenging or impossible to study in vivo. Our goal is to leverage an understanding of these responses, both immediate and longer-term (e.g. anti-tumor immune responses) in order to improve treatment for cancer patients.

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We are currently working in collaboration with the Davalos lab in SBES, and Dr. John Rossmeisl in Vet Med, to quantify the cell specific responses to therapeutic electric field treatments, in the context of the heterogeneous glioma microenvironment. Above we show a demonstration of tumor ablation specificity (lower death threshold for U-87 tumor versus normal human astrocytes (NHA) in a 3D microwell brain tumor model, illustrating the cell type-dependent variations in cell death resulting from high amplitude, high frequency electric field exposure (lesions shown with live-dead staining).

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Related recent papers:
Irreversible electroporation inhibits pro-cancer inflammatory signaling, Bioelectrochemistry, 2017

Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment, Cancer Letters, 2016

Targeted cellular ablation based on the morphology of malignant cells, Scientific Reports, 2015
Funding:

The electric field project is supported by the National Cancer Institute of the National Institutes of Health under award numbers R21CA192042 and R01CA213423.

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