The SU2C-BCRF Cancer Convergence Dream Team Progress Update
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The SU2C-Breast Cancer Research Foundation Cancer Convergence Dream Team Progress Report
“Ecology of the Tumor Microenvironment in Breast Cancer”
Grant Funded: January, 2016
Funding: $3.67 million
Convergence Team Leader:
• Peter Lee, M.D., Beckman Research Institute of the City of Hope
• Mickey Atwal - CSHL
• Darrell Irvine - MIT
• Herbert Levine - Rice
• Clare Yu - UCI
Through collaboration of research scholars in distinct disciplines, convergence grants offer a novel model research meant to spur innovation in new ways of combating cancer. By taking advantage of advances in information technology, nanotechnology, new material research, imaging, optics, quantum physics, and other physical sciences, often considered outside the realm of traditional biomedical research, the subsequent convergence grants may provide critical outcomes to advance the fight against cancer.
Tumors consist not only of cancer cells, but also normal supporting (stromal) and immune cells that together, create the tumor microenvironment. Cancer cells can take on dramatically different properties based on the microenvironment, the clinical impact of which is only recently becoming appreciated. In many different cancer types, including triple-negative breast cancer (BC), tumors with higher stromal fractions portend worse clinical outcomes. In contrast, tumors infiltrated by immune cells have better clinical outcomes.
The Team is approaching the tumor microenvironment from a new perspective. Instead of focusing on individual components, the Team is thinking about the microenvironment as an ecosystem of cell populations and supportive tissues. The complex interactions of the microenvironment ecosystem may lead to emergent properties of the tumor which would otherwise be obscured. An understanding of these properties may allow investigators to devise new treatment approaches that destabilize the ecosystem while leaving healthy cells unaffected.
The Team is combining sophisticated imaging techniques, 3D cell cultures, bioinformatics, ecology modeling, nanotechnology, and cell culture using patient samples to develop a detailed understanding of the tumor microenvironment in triple-negative breast cancer. To that end, the Team has three specific aims:
1. Detailed characterization of the breast cancer tumor microenvironment compared to normal tissue. The team is creating 3D maps of all the cells in the tumor microenvironment, examining the distribution of cell types, blood and lymph vessels, and collagen, and sequencing RNA from specific populations of cells within the microenvironment to better understand the molecular mechanisms that support different parts of the tumor.
2. Dissect ecological interactions via 3D cultures. The Team is growing 3D cultures of cancer and stromal cells obtained directly from patients and growing cultures with different combinations of cell types to create systems that can be used to test ecology models computationally constructed from the data obtained in aim 1. The goal is to devise new ways to influence the tumor microenvironment to limit or eliminate tumor growth.
3. Test therapeutic and imaging applications focused on the tumor microenvironment. Here, the team is investigating ways to direct treatment to different cell types to destabilize the tumor microenvironment.
The Team has visualized tissue sections of breast cancers, identifying regions of relative density for different cell types and collecting material for single cell sequencing. Computational methods for modeling the tumor microenvironment are being developed. Cell cultures have been successful grown and are being analyzed. Finally, new therapeutic strategies for remodeling the tumor microenvironment using nanoparticles to target compounds to specific areas using mouse models is underway.