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Institute for Computational Medicine Distinguished Seminar Series 2016-2017
April 4 @ 11:00 am - 12:00 pm
Steering Cancer Evolution: Harnessing Phenotypic Heterogeneity to Design Better Therapies
Dr. Alexander R.A. Anderson
Co-Director of Integrated Mathematical Oncology (IMO) and senior member
Moffitt Cancer Center & Research Institute
Heterogeneity in cancer is an observed fact, both genetically and phenotypically. Cell-to-cell variation is seen in all aspects of cancer, from early development to invasion and subsequent metastasis. This heterogeneity is also at the heart of why many cancer treatments fail, as it facilitates the emergence of drug resistance. The complex spatial and temporal process by which tumors initiate, grow and evolve is a major focus of the oncology community and one that requires the integration of multiple disciplines. Tumor heterogeneity at the tissue scale is largely due to ecological variations in terms of the tumor habitat driven by spatially heterogeneous vascularity, which is readily observed on cross sectional imaging. Molecular techniques have historically averaged genomic signals from large numbers of cells obtained in a single biopsy site, thus smoothing and potentially hiding underlying spatial variations. The complex dialogue between tumor cells and environment that produces intra- and inter-tumoral heterogeneity is fundamentally governed by Darwinian dynamics. That is, local micro- environmental conditions select phenotypic clones that are best adapted to survive and proliferate and, conversely, the phenotypic properties of the cells affect the environmental properties. While these complex interactions have enormous clinical implications because they promote resistance to therapy, the dynamics are impossible to fully capture via experimentation alone.
Here we present an integrated theoretical/experimental approach to develop dynamical models of the complex multiscale interactions that manifest as temporal and spatial heterogeneity in cancers and ultimately govern tumor response and resistance to therapy. Specifically, we examine the impact of micro-environmental modulation on cancer evolution both in silico, using a hybrid multiscale mathematical model, and in vivo, using three different spontaneous murine cancers. These models allow the tumor to be steered into a less invasive pathway through the application of small but selective biological force. Our long term goal is explicitly translational as we focus our integrated approach on an emerging cancer treatment paradigm that actively harnesses evolutionary dynamics to improve patient outcomes.
Clark Hall 110 (Homewood Campus)
Video-teleconferenced to Traylor 709 (Medicine Campus)
Lunch will be provided at 12:00 PM (Homewood location only)