When Cancer Glows

By Drs. David Niesel and Norbert Herzog, Medical Discovery News

When surgeons remove a cancerous tumor, their goal is to remove all of it. But determining which cells are cancerous and which are healthy is tough. A pathologist's job is to quickly examine the excised tissue to determine whether all of the tumor has been removed. Sometimes, despite a medical team's best efforts, later MRI and CT scans reveal that cancer cells have been left along the margins. As a solution, scientists are looking for ways to light up cancer cells so that surgeons can see them more easily during an operation.

Scientists at the Massachusetts Institute of Technology invented a blue fluorescent dye called LUM015. They injected the dye into 15 breast cancer patients at the Duke University School of Medicine before surgery. The doctors were able to successfully remove the tumors in each of these women, and none of them experienced any adverse reactions.

The dye, LUM015, works because it is cut by a protease enzyme called cathepsins. In normal cells, cathepsins' job is to cut and degrade proteins. However, in many tumors, cathepsins are made in higher amounts and are sometimes secreted by cells. Once secreted, these cathepsins rest on the surface of cell and then serve as a marker to identify tumor cells.

These extra cathepsins also begin to digest the extracellular matrix or ECM. The ECM is a mesh of molecules that holds cells in place. Once the ECM is gone, cells lose their ability to stay in one place and start migrating into the surrounding tissue, a hallmark behavior of cancer cells. In fact, one of stages of cancer is called metastasis, which happens when cancer spreads to other parts of the body.

When these extra cathepsins on tumor cells cut LUM015, the dye causes them to light up blue. A surgeon can see this blue luminescence when a handheld imaging device is held over the area. In experiments with mice, the tumor tissue with LUM015 glowed five times more brightly than normal tissue making even small amounts of tumor easy to spot.

About 40 percent of cancer surgeries require a second surgery. This is because the tumor removal did not result in sufficient margins around the tumor free of cancer cells. Since the goal of every cancer surgery is to remove all of the tumor, LUM015 could help ensure this. It is the first protease-activated dye for cancer detection during surgery that has been tested for safety and effectiveness in humans. So far, it seems to be working as everyone had hoped. The goal is to test the dye in more patients and at additional hospitals to determine its safety and assess its ability to aid in the removal of all tumor tissue on a larger scale.

The scientists who invented LUM015 started a company called Lumicell. They hope to save people from the pain and cost of extra surgeries and potentially the amount of radiation therapy used to ensure that all tumor cells were eliminated the first time.

Medical Discovery News
is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.