Nanotechnology-Based Targeting of Breast Cancer Liver Metastases
Abstract
This project develops a system to predict the effect of macrophage-delivered therapy on liver lesions based on tissue samples or histological slides taken from patient-resected tumors. This will help to efficiently personalize this nanomedicine-based therapy. The project will: (1) evaluate ability of different breast cancers (including commercially available human cell lines and clinically derived tumors from patients) to recruit macrophages in vitro in three dimensional breast tumor spheres, which resemble poorly vascularized liver tumors; (2) test the correlation between the number of macrophages in primary tumors and in distant tumors in the liver in vivo and in clinical samples from patients, and the ability to take up and slowly release nanotherapeutics; (3) apply computational modeling to fine-tune therapy schedules and quickly predict response based on patient tumor-specific analysis of macrophages and other markers in the tumor microenvironment. In this project period the HMRI team (Godin) focused on in vitro studies in 2D and 3D cancer cell lines and PDX as well as obtaining ACURO and HRPO approvals, finding clinical samples and initiating the analysis as well initiation of validation of mathematical model of tumor growth with U of L team. The U of L team (Frieboes) focused on development of a mathematical model of metastases that could efficiently simulate tumor growth and response to treatment. To this end, the numerical solution of the 3D model was implemented with a distributed computing approach. Further, an immune system component was implemented to simulate biologically-relevant tumor-immune interactions in the metastatic microenvironment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2022
- Accession Number
- AD1170066
Entities
People
- Biana Godin
- Hermann B Frieboes
Organizations
- University of Louisville