The excitement in the lab was palpable as Dr. Matthew Gdovin, associate professor in the Department of Biology at UTSA, described the ground-breaking research that may change the way we treat cancer. This new treatment, Photodynamic Therapy, causes no side effects and is effective in killing some of the most difficult to cure cancers.
Many of us have seen someone struggle through cancer treatments, often wondering if the treatment would kill before the cancer did. Chemotherapy and radiation may kill the cancer cells, but healthy cells don’t always escape. Besides hair loss, patients may suffer from nausea, severe pain, fatigue and much worse.
Not all cancers can be treated with current methods: tumors on the spine, brain stem, or the aorta can’t be removed surgically. Triple Negative Breast Cancer is resistant to most chemotherapies because the tumors don't have the target receptors. Cancer that has returned after earlier treatments is often no longer susceptible to the drugs used.
What then, if we had a treatment that could target a hard to reach tumor, destroy it, but leave the rest of the body healthy?
When a cell becomes too acidic, it kills itself in a process called "apoptosis." Chemotherapy makes the cancer cell more acidic, but it makes other cells acidic too, causing the painful side effects. The trick then is to target only the cancer cells, forcing those cells to kill themselves, but keeping the others alive.
Gdovin and his team have discovered a way to do just that. Nitrobenzaldehyde (NBA) is a harmless chemical compound that passes easily into a cell through diffusion. The chemical has no effect on the cell on its own. Similarly, when a beam of light is shined onto a normal cell, nothing happens. But when NBA is there, that beam of light breaks up the compound, creating an acidic environment which signals to the cell to commit suicide. They saw this happen when they injected cancer cells with NBA and a fluorescent dye, which allowed them to measure the pH optically. Forty minutes after flashing the NBA-treated cells with a beam of light, only the NBA-treated cells began to die, which could be seen as the fluorescent colors disappeared.
In December of 2014, the team moved on to animal models, working around the clock for 90 days. They induced a tumor in the mice and after it had grown large enough to be visible, they injected NBA directly into the tumor. After waiting one hour, long enough to allow the chemical to make its way into the tumor cells, they used a laser to flash light onto the NBA-infused tumor cells. Shining the light anywhere else had no effect on the animal, but those cancer cells with NBA died, shrinking the tumor. Further studies showed that by treating repeatedly, the tumor diminishes almost completely. This new technique, photodynamic therapy, relies on both the light and the chemical.
By targeting only the cancer cells, the healthy cells are not affected. Even if the NBA has infused into the cells, as long as they don't receive the light treatment, nothing happens. As a result, photodynamic therapy has none of the harsh side effects of typical cancer therapies. However, it requires that the tumor be visible, so isn't applicable to all cancers.
“We’re targeting the most unmet needs: tumors that can’t be operated on, aren’t subject to irradiation, or when the patient is too sick to have surgery,” Gdovin said. These are some of the hardest to treat cancers.
As his lab continues studies to move photodynamic therapy to FDA approval, Dr. Gdovin is looking to new ways to treat cancer that has spread to other parts of the body. Some cancers over express specific molecules. By developing nanoparticles that recognize these molecules, only the cancer cells will take up the nanoparticle. Using a laser that can pass through several layers of tissue including bone, such as in the brain, the light will activate the cancer-killing nanoparticle, leaving the healthy cells unaffected. This research is still in the early phases, but has shown promising early results.
Dr. Gdovin is quick to acknowledge the contributions of his team, a collection of 18 undergraduate, post-baccalaureate and graduate students. Standing in the lab it’s hard not to be filled with excitement as the team pushes to new scientific discoveries. Larger than most university labs, the students undergo a rigorous process to join. They must review and present components of a research paper, and the current students each have a vote to add the new student to the team. The more experienced students mentor the newer students, preparation for what they'll do when they have their own labs one day.
“Straight As are less important than showing motivation and a passion for science,” Gdovin said. It is that motivation which makes this research possible, particularly when it requires around the clock efforts for 90 days.
Scientific discovery requires creativity and innovation, as well as an understanding of the practical applications of those discoveries. UTSA Master’s student Zack Jordan and Dr. Gdovin won an Innovation Corps Grant from the National Science Foundation (NSF), which teams students with academic researchers and business mentors to foster entrepreneurship bringing new technology to commercialization. As part of the process, the team interviews individuals who will be impacted by these discoveries: patients, scientists, medical professionals, and industry representatives. When it came to cancer, the overwhelming message was clear: they want a less toxic way to treat it.
With photodynamic therapy, they may have found a way.
*Top image: Student researchers Nuha Kadri and Nizar Alyassin record their findings. Photo by Scott Ball.