Understanding cancer metabolism

Joseph Ippolito

Every living entity — whether it’s human being, a bacterium, or a cancer cell — needs energy to survive. Joseph E. Ippolito, MD, PhD, instructor in radiology, believes that by identifying specific metabolic — or energy-related — features of a cancer cell that allow it to survive, researchers may be able to selectively kill cancer cells in patients.

Ippolito has discovered a new metabolic pathway in cancer cells that is activated by stress and directly correlates with poor outcomes in multiple cancers. The pathway involves the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA).

According to Ippolito, metabolism can change if a cancer cell becomes “stressed.” For example, in a large tumor where cancer cells are constantly dividing, they need a steady supply of oxygen and nutrients to survive. “Crowded” cells in the center of the tumor may not have access to these critical elements and become “stressed” to the  point where their metabolism changes to adapt to these new conditions. As a result, chemotherapy and radiation therapy may not have as significant an effect on these tumor cells. In addition, the cells have a higher propensity for metastasis.

Ippolito’s interest in the metabolic features of aggressive cancers is nothing new. He earned his undergraduate degree in biochemistry from Cornell University and graduated from Washington University School of Medicine’s MD/PhD program with a PhD in molecular biophysics in 2007. As a graduate student, he worked on several cancer metabolism-based projects and continues that research today.

In 2013, Ippolito received a one-year, $40,000 Seed Grant from the Radiological Society of North America (RSNA) to study “Metabolic Characterization of the Neuroendocrine Cancer GABA shunt.” Data from the project will indicate the feasibility of the research prior to applying for funds from other agencies.

After receiving his MD/PhD, he completed residency training and a fellowship in Body MRI. Today, he spends about 80 percent of his time conducting research and the balance on clinical service doing predominantly MR and CT imaging. His focus is on oncologic imaging, with an interest in prostate MRI.

The blending of his expertise in biology, chemistry, and imaging has proved beneficial. To understand how the pathway he discovered allows cancer cells to survive, Ippolito is using a combination of optical, MR, and nuclear imaging in conjunction with advanced chemical and genetic techniques. He also is using this information to develop novel approaches to treating aggressive cancers, such as with the use of FDA-approved pharmaceuticals.

“My goal is to make advancements in cancer metabolism at the bench and to take those discoveries to the clinical setting,” says Ippolito. “We can do that by developing new imaging techniques that will allow physicians to detect aggressive disease, stratify patients based upon severity of the disease, and identify molecular details about the cancer that can be used for therapeutic purposes.”