Scientists know that genetics and the interactions between cancer cells and the extracellular matrix (ECM)—the scaffold-like material between cells that gives the cells structure—have a big influence on tumor growth, metastatic potential, and drug resistance. However, their understanding of these interactions in living organisms is limited because the ECM's composition is very complex.
Working with researchers at the Mayo Clinic, Illinois Bioengineering Assistant Professor Gregory Underhill developed an engineering-based tool that helps unravel the ECM's composition and underlying mechanisms that enable cancer to spread and become resistant to chemotherapy and other treatments.
Specifically, the researchers developed a cell microarray platform that they used to analyze lung cancer drug responses within certain ECM microenvironments. They determined that ECM proteins together with ASCL1, a protein that can result in the development of small cell lung cancer, changed how tumor cells respond to certain drugs.
Based on this work, Underhill and his team recently received a two-year $375,000 National Institutes of Health/National Cancer Institute R21 grant to apply their high-throughput method to further studies. According to Underhill, they will use the microarray to print multiple combinations of proteins and to miniaturize cell cultures. In addition, they will change the conditions to test whether the cancer cells will respond better or worse.
“We are really interested in following up with questions such as: Why does that happen? What are the changes that happen within the cancer cells in these environments that cause them to be sensitive or resistant to a drug?” said Underhill.
The research can lead to diagnosing better cancer treatments for patients. Biomarkers can be created to test whether a patient would be more sensitive or resistant to different types of therapies by knowing how the proteins influence cells to respond to drugs.
“The idea there is that, potentially, if you study what proteins are in a tumor and how they change from person to person and if you already know that those proteins influence how the cells respond to drugs, then you can correlate this to how the patients will respond to different treatments,” explained Underhill.
In addition to Underhill, the grant team includes Mayo Clinic co-investigators Farhad Kosari and Mariza de Andrade.
“Whenever you are looking at gene expression or proteins in tumor samples, you often aim to correlate these measurements with patients’ survivals and other indicators," said Underhill. "There are large-scale studies that have a lot of data, and we are excited to work with very experienced collaborators.”