Cancer research can be viewed as a chase—a plodding, methodical relay in which researchers collectively work toward slowing or even stopping the spread of cancerous cells. Though breakthroughs have been made, diagnoses continue. This includes breast cancer, the second-leading cause of cancer-related deaths in women.
Temple University Assistant Professor of Bioengineering Bojana Gligorijevic has been part of the chase, beginning as an analytical chemist in her native Serbia and then pursuing a PhD in biophysics at Georgetown University and postdoctoral research in cancer microscopy at the Albert Einstein College of Medicine. Now, Dr. Gligorijevic is looking to leverage a $2 million research award from the National Cancer Institute of the National Institutes of Health, to deliver new breast cancer predictive diagnostic tools.
For most breast cancer patients, complications are driven by metastasis, which occurs after a tumor cell exits the primary tumor. Once metastasis happens, there is often no turning back.
"Treatment is much harder at that point," Dr. Gligorijevic said.
Another part of the chase is cell motility: the speed at which tumor cells follow individual collagen fibers to reach blood vessels.
"We have a unique, intravital systems microscopy approach that I developed in collaboration with systems biologists," Dr. Gligorijevic said. "It is based on recording tumor cell motility in real time inside the tissue. It has identified two different migratory behaviors that tumor cells exhibit: one is of them essentially running along collagen fibers. The other behavior includes invadopodia—small, finger-like cellular protrusions that cause collagen degradation around the blood vessels. Once invadopodia create an opening in the blood vessel, the tumor cell enters the vessel and eventually metastasizes."
Working with a number of researchers at Fox Chase Cancer Center, Dr. Gligorijevic will be using patient samples to develop biomarkers based on invadopodia. They will capture videos of fluorescent tumor cells labeled so invadopodia 'glow' in cyan, while their nuclei glow in changing colors following their progression from cell birth to cell division. Video recordings are automatically tracked and classified by machine learning.
"We were able to further show that in mouse models, removing invadopodia completely stopped metastasis. Now, we are interested in finding ways to remove invadopodia from tumors without affecting any other cells. Invadopodia can only form in cells before they start dividing. So, if you try to stop cell division and tumor growth by chemotherapy, you might increase the invadopodia number and cause metastasis," Dr. Gligorijevic added.
How could this be important for breast cancer patients?
"We are hoping this predictive diagnostic can help inform future preventative therapy," Dr. Gligorijevic said. "If we demonstrate our invadopodia-based biomarker is successful in predicting metastasis, a patient exhibiting high invadopodia frequency could first be treated with an invadopodia inhibitor, and only then with chemotherapy, such as a cell cycle inhibitor, as a sort of combination therapy. Otherwise, if they get a cell cycle-only treatment, their invadopodia count would skyrocket and you'll likely see metastasis five or 10 years down the road."