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Modeling tumor-microenvironment interactions for development of biophysics-informed strategies in cancer therapeutics
April 24, 2017 @ 4:00 pm - 5:15 pm
Cancer progression is regulated not only by the molecular biology and genetics of the disease but also by the physical properties of the tumor and surrounding tissues. In particular, the development of mechanically rigid fibrous stroma is a defining feature of many solid tumors and has been shown to play complex roles both promoting and constraining malignant growth behavior. It remains poorly understood, however, how this altered mechanical landscape, which is dynamically remodeled during tumor progression and invasion, regulates susceptibilities to cancer therapeutics.
Several projects in our group examine how biophysical interactions with the tumor microenvironment impact upon phenotypic changes which determine therapeutic response. This work is enabled by the use of in vitro 3D tumor models with tunable and rheologically-characterized extracellular matrix (ECM). Combined with imaging-based analyses of phenotype and in situ microrheology measurements of dynamic matrix remodeling, this platform provides a means to co-register rigidity-dependent cell shape, mechanics, and motility with response to therapeutic intervention. In this context, we specifically contrast classical chemotherapy agents with photodynamic therapy (PDT), in which light activation of a photosensitizing agent leads to cell death by local generation of reactive oxygen species. Interestingly, our recent results show that while modulation of ECM composition to promote increased cell motility imparts resistance to chemotherapy, the same chemoresistant populations exhibit increased sensitivity to PDT. These and other emergent findings will be discussed in the broader context of connecting cancer biophysics with cancer therapeutics.
Tea and coffee will be served at the speaker’s reception in the Chapman meeting area 3:30 pm.
The student Questions and Answers will be held in Phillips 277 after the colloquium from 5:15 – 6 pm.