Speaker
Description
Drug delivery in solid tumors is a major challenge due to the complex tumor microenvironment. Abnormal vasculature, a dense extracellular matrix (ECM), and elevated interstitial fluid pressure (IFP) hinder the penetration of therapeutic agents [1]. ECM-modifying therapies have been proposed to overcome these barriers by altering the structure of the ECM and improving drug transport in tumor tissue [2].
In this study, we develop a dynamic mathematical model of the tumor microenvironment to examine how ECM-targeted therapies influence drug delivery. The model incorporates key components of the tumor microenvironment, including tumor cell density, vascular dynamics, IFP, oxygen transport, and drug distribution. Within this framework, we investigate PEGPH20, a hyaluronan-depleting agent, to determine how hyaluronan (HA) degradation modifies the tumor microenvironment and affects drug transport.
Model simulations show that combining ECM-targeted therapy with chemotherapy improves intratumoral drug penetration compared with chemotherapy alone. Furthermore, the results suggest that appropriate treatment dosing and scheduling can enhance therapeutic outcomes. The proposed model provides a computational framework for exploring ECM-targeted treatment strategies and identifying conditions that improve drug delivery in solid tumors.
Bibliography
@article{fukumura2007,
author = {Fukumura, Dai and Jain, Rakesh K.},
title = {Tumor Microenvironment Abnormalities: Causes, Consequences, and Strategies to Normalize},
journal = {Journal of Cellular Biochemistry},
year = {2007},
volume = {101},
number = {4},
pages = {937--949},
month = {Jul},
}
@article{huang2021,
author = {Huang, J. and Zhang, L. and Wan, D. and et al.},
title = {Extracellular Matrix and Its Therapeutic Potential for Cancer Treatment},
journal = {Signal Transduction and Targeted Therapy},
year = {2021},
volume = {6},
pages = {153},
}
