Atsuo Sasaki, PhD, an Assistant Professor in the Division of Hematology-Oncology, is creating a platform for rigorous study of the complex biochemistry that underlies the rapid growth of metastatic brain tumors. His work is a core component of the Brain Tumor Molecular Therapeutics Program, which seeks to understand the biological mechanisms of cancer’s spread to the brain and to translate that knowledge into more effective treatments. The effort is a partnership between the University of Cincinnati Neuroscience Institute and University of Cincinnati Cancer Institute.
In particular, Dr. Sasaki is zeroing in on the energy-guzzling nature of metastatic brain tumors, which differentiates them from normal brain cells as well as from metastases in other parts of the body.
“Normal cells in the brain don’t grow in number,” Dr. Sasaki explains. “Only tumor cells grow in the brain, expending vast amounts of energy while doing so. In addition, metastatic tumor cells tend to grow faster in the brain than anywhere else. For example, patients with lung cancer often experience their first symptoms as neurologic (rather than in the chest) because of the rapid development of brain metastasis from the primary site. Likewise, some metastasized brain tumors have the ability to divide more rapidly than other types of tumors, and the molecular mechanism for this phenomenon has been largely unknown.”
The secret to that rapid growth is energy utilization, Dr. Sasaki says, and this is the focus of his laboratory.
“Brain tumors grow very fast, and they need a significant amount of energy to accomplish this rapid cell division and proliferation,” he says. “You could liken them to large, gas-guzzling vehicles that use lots of fuel to get where they need to go. And, like gas-guzzling vehicles, these cancer cells in the brain require frequent trips to the gas station to fill up their tank.”
This, Dr. Sasaki says, is an inherent vulnerability and offers a potential opportunity to scientists. He explains that just as an automobile has an energy indicator – the fuel gauge – cancer cells also have an indicator of how much fuel they have remaining. If cells can be tricked into ignoring their fuel indicator, or if they can be tricked into thinking their fuel tank is full when in fact it is empty, they will die.
“If we can keep the tumor cells from going to the gas station for more fuel, they will expire,” Dr. Sasaki says. “We know that if this system is broken – if the cells run out of gas – they are going to die.”
Dr. Sasaki’s lab also will be studying the “soil and seed” aspect of metastatic brain tumors. Once a brain metastasis has taken root in the brain, it requires nutrition to grow. Cancer cells adapt so that they can utilize available nutrition. Preventing that adaptation, or preventing nutritional utilization, could be another path toward shutting down the ability of a brain metastasis to grow.
Once Dr. Sasaki develops a clear understanding of how cancer cells draw nutrition from the brain and how they know when to “return to the gas station for more energy,” he has the potential to translate his knowledge into treatments that can be tested in Phase I/II clinical trials by the UC Brain Tumor Center’s clinical team.
Dr. Sasaki brings a broad-based scientific background to UC. He was recruited from Harvard University, where he was an Instructor in Medicine. He earned his doctorate in molecular biology from the Kurume University School of Medicine in Kurume City, Japan, where he focused on cytokine signaling, the intercellular communication among protein molecules. His post-doctoral work, performed at the University of California, San Diego, focused on immune cell migration and tumor cell invasion.
“I have rigorous training that ranges from biochemistry to oncogene signaling,” Dr. Sasaki says. “I believe I have a unique viewpoint of cancer, and I hope to use that viewpoint to develop a robust brain tumor research program here at the UC Brain Tumor Center.”
While at Harvard, Dr. Sasaki was part of a research team that discovered a new mechanism by which a cell protein known as Ras can trigger persistent signaling, which can lead to cancer. An article about those findings was published online in three prestigious journals: Science Signaling (2011), Cancer Discovery (2011) and Nature Structural Molecular Biology (January 2013).