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Applied Math Seminar
Biocomputational and Experimental Modeling of Cancer and Chemotherapy
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This research focuses on the biocomputational and experimental modeling of cancer tumor growth and therapy. To this end we have created a sophisticated in silico tumor simulator. Our goal is to customize cancer drug therapy in the clinical setting by using tumor information specific to each patient. This approach should not only save time and resources in cancer treatment, but also be most beneficial to the patient. Our multiscale, multidimensional tumor simulator has the capability of showing cancer progression through the stages of diffusion-limited dormancy, vascularization and rapid growth, new equilibrium, and tissue invasion. This simulator encompasses some of the main physical laws of cancer growth and creates an in silico system that exhibits combined two-dimensional tumor growth and angiogenesis. The system captures the complicated morphology and connectedness at the tumor/tissue interface, including invasive fingering, tumor fragmentation, and healthy tissue degradation. Angiogenesis is included as a continuous feedback process involving tissue growth and nutrient demand. Here, we use the tumor simulator to demonstrate fundamental transport limitations in delivering anticancer drug into tumors, whether this delivery is via free drug administration or via nanoparticles injected into the bloodstream. In the case of nanoparticle delivery, making some assumptions regarding targeted delivery, we find that host tissue toxicity can be less than that of traditional delivery, and also further investigate the effect of anti-angiogenic "normalizing" in ameliorating transport limitations. Our results indicate that fundamental transport limitations apply to both traditional and nanoparticle drug delivery. Even in a best-case scenario involving an homogenous tumor of one drug-sensitive cell type, targeted nanoparticle delivery, low host tissue toxicity, and sufficient drug concentration to rapidly kill all cells in vitro, the in vivo rate of tumor shrinkage can be as low as several orders of magnitude less, and the tumor may achieve a new mass equilibrium far above detectable levels. In collaboration with the UCI Medical Center, we are developing experimental models to study the effects of chemotherapy on specific in vitro and in vivo cancer tumor tissues. This work will yield data that will be used as input to the tumor simulator and provide a sound biological foundation for the biocomputational model. |