7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
Physical Dynamics of Cancer Response to Chemotherapy in 3D Microenvironments: A Platform to Examine Complex Physical and Chemical Microenvironments
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Recent advances and successes in microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may significantly augment the current development of new model systems for toxicology, systems biology and oncology allowing for dynamic monitoring of tissue behavior. Tissue microenvironment, especially within the tumor, is highly complex and can evolve not only during tumor outgrowth but also when anticancer treatments are administered.
In vivo, tumor behavior is modified by its own microenvironment receiving cues through structural information by surrounding extracellular matrix (ECM), and through the surrounding chemical nature such as the state of oxygenation or acidity. The microenvironment of advanced tumors is frequently hypoxic due to a variety of factors that result in abnormal vasculature with reduced oxygen transport and increased diffusional space between tissue compartments. Another defining feature of malignant tumors is enhanced glycolysis that leads to production of lactate and H+ ions, resulting in an increasingly acidic environment. As a result, the type of tumor microenvironmental selects for tumor cells that can thrive within these harsh conditions and profoundly impacts anti-tumor drug efficacy. We are developing a new computationally driven platform to examine these complex physical and chemical microenvironments utilizing organ-on-chip microfluidic bioreactor technology coupled with a predictive mathematical model of tumor growth and therapeutic response. This integrated platform combines the power of organ-on-chip 3D tissue bioreactor, developed to include uniform and non-uniform fully controlled physical and chemical microenvironments, together with a 3DMultiCel math model that allows predictive testing of a broad range of microenvironmental combinations around the experimentally validated baseline. We are applying this technology to applications of anti-tumor drug efficacy of mammary tumors under mixed microenvironments as well as toxicant evaluation on normal mammary development including hyperplasia assessment.