Modulating Tumor Cell Extracellular Vesicle Signaling for Therapeutic Intervention and Monitoring

Abstract

The discovery that tumor cells discharge vast quantities of extracellular vesicles (EVs) that contain functional molecules which promote immune modulation and drug resistance, urges the need for novel therapeutic interventions. Here we take an approach based on the EV-release-modulation strategy to treat tumors, suppress their spread, and monitor the therapy efficacy. We propose a molecular communication (MC)-based system model to implement the oncogenic EV release modulation and monitor the EV spatiotemporal biodistribution. The proposed system uses drugs which target the tumor cell pH regulatory biochemical mechanisms. We develop a comprehensive computational framework where we integrate adapted and extended versions of the biophysical model of tumor cell pH regulation, the tumor cell proliferation model, and our previously developed MC model of pHe-dependent EV biodistribution. We fix specific parameter values of the system model by combining available experimental data performed in diverse tumor cell systems. Using the developed system, we analyse the dynamics of intracellular pH (pHi), extracellular pH (pHe), tumor cell growth pattern, and EV release and biodistribution. Our proposed system and computational framework can be used as a tool to track the oncogenic EV biodistribution, which can be used as a biomarker to monitor the tumor and optimize anticancer therapy.