A Different Approach
Meet four researchers who choose to outsmart cancer by thinking outside the box.
- Painting By Numbers
Pablo Picasso once joked that computers were useless because all they could do was give us answers. But the man who revolutionized art could not have foreseen just how many lifesaving answers are provided by today’s computers nor the way information technology has revolutionized medicine.
André Rogatko, PhD, relies on computer science and biostatistics–the gathering of genetic and other screening data–to create customized drug regimens that fight cancer more effectively and with fewer side effects than ever before.
“While there is no way to personalize chemotherapy drugs for every individual, we can determine with good precision how groups of people will respond to a medication dose,” explains Dr. Rogatko, director of the Biostatistics and Bioinformatics Research Center. The idea is to create different biological profiles and analyze which dose fits best.
The amount of data that must be gathered and the complexity of mathematical modeling are staggering. “What we are doing would not have been possible a few decades ago,” Dr. Rogatko says. Sophisticated software is used to process huge volumes of data, which might include details about immunity, DNA, and a host of other patient-specific biological information.
Dr. Rogatko, who earned his doctorate in genetics and statistics, specializes in the use of biostatistics in clinical trials. “Most dose-finding trials are still done in the conventional way, using a predetermined set of drug doses,” he says. That approach provides the optimal dose to patients only 35 percent of the time. On the other hand, studies show that using biostatistics to dynamically tailor treatment identifies the optimal dosage 55 percent of the time.
“That’s an important difference,” says Dr. Rogatko. “If we keep innovating at that pace, we can overcome cancer.”
- Great Barrier Relief
Millions of men take erectile dysfunction drugs to restore lagging love lives. But could those little pills also save lives? “Studies suggest the answer may be ‘yes,’” says Julia Ljubimova, MD, PhD, who is investigating the potential use of erectile dysfunction drugs such as Levitra® for the treatment of brain tumors.
Chemotherapy drugs targeted at breast or lung cancer reach those tumors quite efficiently. But the brain is more complicated, explains Dr. Ljubimova, director of the Nanomedicine Center in the Department of Neurosurgery. The brain is protected by the blood-brain barrier, or BBB, formed by tightly connected cells. The BBB keeps harmful substances out. Unfortunately, it also prevents chemotherapy drugs from reaching the brain tumors they are meant to attack. While the BBB behaves somewhat differently around brain tumors than it does with healthy tissue, it still circumvents the delivery of anticancer medication. Enter erectile dysfunction drugs.
As part of a team led by Keith Black, MD, chairman of the Department of Neurosurgery, Dr. Ljubimova and her colleagues found that Levitra helped the cancer-fighting drug Herceptin® better penetrate the brain in a mouse model. Levitra creates a chemical reaction in the bloodstream that relaxes the vessels supplying blood to the brain, creating a window of increased leakiness in the BBB that doubles the amount of chemotherapy reaching a tumor. In initial, preclinical animal studies, survival rates increased by 20 percent when erectile dysfunction drugs were used together with the chemotherapy agent, compared to chemotherapy alone. Clinical trials are now under way.
Adds Dr. Ljubimova, “It would be incredibly helpful if one of the world’s best-selling drugs, already proven safe, could be added to our arsenal against one of our most feared diseases.”
- The Light Brigade
A brain cancer diagnosis is a bleak thing. Among the many treatment challenges is the fact that it’s extremely difficult for neurosurgeons in the operating room to distinguish between healthy brain tissue and cancerous tissue. But there is light at the end of the tunnel: fluorescence spectroscopy.
Cedars-Sinai researchers have developed imaging technology that not only makes removing brain tumors safer and more effective, but could also improve early detection.
“When you shine a flash of light on various molecules, they send different colors back to you,” explains Pramod Butte, PhD, assistant professor in the Department of Neurosurgery. “The color—or fluorescence spectrum—tells us a lot about these molecules.” Scientists can analyze the color in real time to determine whether it signals healthy or cancerous cells. Researchers focus on the intensity of the fluorescence and the duration of the flash. For example, a high-grade tumor—one that is poorly differentiated or undifferentiated from normal cells and that is likely to grow rapidly—sends back light that lingers a little longer compared to normal tissue.
In the operating room, a medical team can use an optical probe about the size of a ballpoint pen to shine a light on brain tissue. When the molecules re-emit light, the properties are captured and analyzed by a data-processing system. While early work has focused on brain cancer, the technology should be applicable to other cancers as well.
As the technology becomes more refined and miniaturized, it may one day also change how we screen for cancer. “With time-resolved fluorescence spectroscopy, we’ll be able to detect cancerous tissue such as breast tumors noninvasively, making biopsies a thing of the past,” says Dr. Butte. “This is a revolutionary and very exciting innovation.” One could even call it illuminating.
- Going Viral
Five years ago, Alain Mita, MD, and his wife, Monica Mita, MD—co-directors of the Experimental Therapeutics Program at the Samuel Oschin Comprehensive Cancer Institute—encountered a radical idea: A virus might be useful in fighting cancer. Scientists discovered that a virus known as Reolysin® could be harnessed to kill cancer cells while leaving healthy cells mainly intact.
Reolysin is a live virus that is relatively benign in most people, manifesting itself in flu-like symptoms. Like all viruses, it’s programmed to find an environment where it can reproduce. Healthy bodies are inhospitable: Normal cells easily rid themselves of Reolysin. Cancerous cells, however, do not.
“The virus lodges itself in cancer cells, which possess an abnormality that allows Reolysin to thrive,” explains Dr. Monica Mita. “The virus happily reproduces until it finally annihilates the cancer cells.”
Studies are underway for the use of Reolysin in lung cancer, part of cutting-edge research taking place in the Experimental Therapeutics Program. Says Dr. Monica Mita, “Our goal is to have available a menu of cancer treatments, and to personalize the treatment protocol for each and every patient based on the genetic makeup of their specific tumor.”
“One day, we will win our battle with cancer,” adds Dr. Alain Mita. “Experimental Therapeutics is helping lead us to that longed-for day.”