Mathematical Algorithms Reveal New Information About Aggressive Breast Cancer

Washington University / Kristen Naegle

Kristen Naegle, an assistant professor of Biomedical Engineering at Washington University in St. Louis is performing a detailed study of breast cancer cells, and utilizing mathematical approaches to uncover the mechanism for metastasizing in especially aggressive breast cancers like *HER2.

Currently, breast cancer comes in second as the most common type of cancer and the second leading cancer responsible for cancer-related deaths in American women. HER2-positive breast cancer metastasizes aggressively and quickly than other types of breast cancer. In order to understand why this happens, Naegle used data from previous experiments, lab experiments, and algorithms.

In previous studies, researchers isolate a particular protein that is overproduced by the HER2 gene, referred to as *HER2-overexpression in 20 percent of breast cancers. Naegele’s study to data from signaling molecules in HER2-overexpressing cells and compared them to those of normal, cancer free cells. Algorithms were required to compare the very minute changes and detect patterns in molecules that highly resembled each other.

What they found was that these small changes had dramatic effects on the behavior of cancer. “Despite the fact that individual molecules are highly similar to each other across cell types, we found that small changes in signaling dynamics led to very large changes in the relationships uncovered between groups of signaling molecules,” she explained.

For example, a change in a protein altered the way cells were connected, so that instead of cells clinging to each other at the cell to cell junctions, they instead were able to flow more freely, allowing for faster metastasizing. The mathematical findings were confirmed with lab experiments.

The dataset used in the algorithms came from a ten-year-old study but Naegle takes a different view of to study disease. She said of her method, “It’s a bottom up approach where we look to understand the basic mechanisms of interaction in the cell to find the outcomes.” She then adds “There still remains a wealth of hypotheses from this analysis that may continue to help us understand how *HER2 drives metastasis.”

*HER2/neu (often just shortened to HER2) is a growth-promoting protein on the outside of all breast cells. Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than other breast cancers. Via;

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