To understand breast cancer, it seems, is to understand timing.

Researchers and clinicians have chased breast cancer, a nimble and deadly opponent, since as far back as Egypt in 1500 BC. During much of that time, they have preached early detection. In a practical sense, if a cancer is identified in time, it can be surgically removed or shrunk with chemotherapy. If it's not, and it metastasizes to a secondary site, there is practically no cure.

Temple College of Engineering researchers are looking at new and novel ways to predict metastasis before it happens by using mathematical modeling and visualization of cancerous cell movements and the surrounding connective tissue.

Two publications from PhD student Kamyar Esmaeili Pourfarhangi (above), along with Assistant Professor Dr. Bojana Gligorijevic, seek to draw out extrinsic and intrinsic factors associated with cancerous cell activity.

"Classic chemotherapy targets cells. What we're saying is that you can also target environment," he said. "If you have the numerical values, you can basically deviate the cell from the condition, inhibiting metastasis. So this would be a new venue toward cancer treatment."

In other words, containing the cancer before it spreads. Buying time.

"Previously, we demonstrated that the tumor cells away from the blood vessels are just randomly following thick collagen fibers, which have structure similar to a rope. Tumor cells adhere to collagen fibers and start ziplining randomly around the tumor," Dr. Gligorijevic added.

By following collagen fibers, cells are led into the zone around the blood vessel, where collagen fibers are tightly-knit together. Once the tumor cell hits a crowded environment, it is forced to switch its behavior.

"Around the blood vessel, a tumor cell starts jack-hammering the connective tissue using enzymes and makes little holes within," said Dr. Gligorijevic. In one publication, mathematical modeling charts how the connective tissue properties are affecting these switches between digging and moving. The other looks at how intrinsic factors such as cell growth and division affect motility.

Their work contributes to a collaboration on automated image processing with that includes Andrew Cohen at the Department of Mechanical Engineering at Drexel University, and on mathematical modeling with Aviv Bergman at Albert Einstein College of Medicine in New York. Dr. Gligorijevic also noted a partnership with the Biosample Repository at Fox Chase Cancer Center, where they are also establishing protocols to test published predictions on human breast cancer samples.

"As bioengineers, we want to be able to predict which cells will metastasize based on their behavior in the primary tumor." Dr. Gligorijevic said. "Because once they leave the tumor, it's over."