Tumor Vasculature Modeling and Validation

Blood flow in the vessels over the tumor domain is often complicated, exhibiting various phenomina such as cycles, shunts and dead ends[1]. In order to study the correlation between the vascular and interstitial flows for effective drug delivery, a general physics-based model which includes the tumor vasculature connecting upstream and downstream blood-flow, is required. Previous work in this area has resulted in the development of mathematical models with varying degrees of simplifications and modeling assumptions which balance computational complexity and modeling error[1,2].

Our work in this area seeks to enhance the predictive capabilities of models using clinical data and rigorous methods in global optimization for stronger model-based approaches in medicine. The information obtained through this approach aides in the development of better models and provides deeper insight into the physical behavior of the tumor microenvironment. These highly-predictive validated models are then used within a design framework for tailoring therapeutics and therapy regimens to individual patient attributes optimized for targeted patient outcomes.

Research Products:

  1. Martin, J. D., Panagi, M., Wang, C., Khan, T. T., Martin, M. R., Voutouri, C., Toh, K., Papageorgis, P., Mpekris, F., Polydorou, C., Ishii, G., Takahashi, S., Gotohda, N., Suzuki, T., Wilhelm, M. E., Melo, V. A., Quader, S., Norimatsu, J., Lanning, R. M., Kojima, M., Stuber, M. D., Stylianopoulos, T., Kataoka, K., and Cabral, H. Dexamethasone Increases Cisplatin-Loaded Nanocarrier Delivery and Efficacy in Metastatic Breast Cancer by Normalizing the Tumor Microenvironment. ACS Nano. 13(6), 6396-6408 (2019). DOI: 10.1021/acsnano.8b07865
  2. Wang, C., Martin, J. D., Cabral, H., and  Stuber, M. D, Rigorous Parameter Estimation for Model Validation in Oncological Systems. In Proceedings, AIChE 2018, Pittsburgh, PA, Oct 29, 2018.

References

[1] J. W. Baish, P. A. Netti, and R. K. Jain, “Transmural coupling of fluid ow in microcirculatory network and interstitium in tumors,” Microvascular research, vol. 53, no. 2, pp. 128-141, 1997.
[2] V. P. Chauhan, T. Stylianopoulos, J. D. Martin, Z. Popovic, O. Chen, W. S. Kamoun, M. G. Bawendi, D. Fukumura, and R. K. Jain, “Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner,” Nat Nano, vol. 7, pp. 383-388, June 2012.