The problem with excising cancerous cells from the body through surgery or radiation is that cells can be left behind to act as a seed to a new tumor. In school, we learned that it can take even as little as 30 cells left behind to do exactly that. Recently, physicians and scientists have found ways to make some cancerous cells glow in the dark, making them easier to spot within the human body and thus, easier to take right out in the hands of oncologists.
Scientists at the National Cancer Institute (NCI) are developing new ways to detect “silent” tumor masses, including ovarian cancer and pancreatic cancer. The problem with these types of cancer is that there are normally very few symptoms that arise until the cancers have progressed and metastasized, making early detection and treatment very difficult. In order to address these detection problems, researchers at the NCI, lead by Dr. Hisataka Kobayashi, M.D., Ph.D., are using fluorescent imaging techniques to detect small tumor growths in mice that would not be detected using the cuurent practices.
The first study uses the fluorescent compound called Av-3ROX, which consists of the protein avidin bound to three molecules of rhodamine X, a fluorescent dye that emits a detectable signal when hit with the correct wavelength of light. The joining of avidin to rhodamine X results in the inability of rhodamine X to fluoresce. The genius of this approach is that avidin binds specifically to another protein that is found only on cancer cells. The cancer cells then “digest” the Av-3ROX, which is then broken down inside the cell to the base parts.
When rhodamin X is released from the avidin protein, it is able to fluoresce, resulting in a cancer cell that glows red and is visible to doctors. The advantage to using Av-3ROX over conventional imaging methods like nuclear isotopes, MRI or an “always glowing” fluorescent molecule is that with Av-3ROX, only the cancer cells are producing a signal, and not the surrounding healthy tissue. Further studies with this compound showed that it has a 92% sensitivity in detecting tumors in mice, correctly showing 465 out of 507 metastases with only a 2% chance of a false-positive result.
The problem with using AV-3ROX is that the avidin protein, while working quite well in mice, will produce an immune reaction in humans. The researchers are currently working on ways to make this compound safer for use in humans by joining the binding site for avidin to human serum albumin.
Another fluorescent compound that is safer for humans uses a monoclonal antibody that specifically recognizes a protein receptor molecule on the surface of the cancer cell to both at least 10 molecules of biotin. The second part of this system is a fluorescent molecule that glows brighter when bound to biotin. This two part method of imaging results in 98% specificity in tumor detection, but it is not known if the compound is safe for use in humans.
Finally, a third compound called GmSA-20ROX looks to be the most promising of the three. This molecule is also designed to specifically target tumor cells, and radio-labeled versions have been used in the past. This compound is able to bind to cancer cells more quickly and efficiently than avidin, with a sensitivity approaching 99%.
It is days like today that I am amazed and humbled to be in the same profession as cancer researchers everywhere. As our understanding of tumor biology grows, so does our ability to logically fight it. Studies are currently underway to assess different proteins expressed by tumor cells in comparison to normal, healthy cells, resulting in a “tumor-specific protein profile”. Use of this profile will provide proteins to target and allow the visualization of tumors before they can progress to an untreatable stage.
We should all take a moment to grasp the coolness of this approach, and to applaud these researchers for developing a tool that will allow for the early detection of cancer as well as the elevated hopes of cancer patients everywhere. Great job!