As posited by the Warburg effect, tumors often use glucose in much greater quantities than normal cells. Positron emission tomography (PET) imaging highlights those cells and tissues that guzzle the fuel. This powerful technology is widely available for both clinical care and research at UCLA.
David Shackelford, PhD, uses PET imaging to understand, in real time, how cancer hijacks metabolism. Shackelford, an assistant professor of pulmonary and critical care medicine, wants to know how certain drugs affect the glucose consumption scan, done in humanized lung cells in mice.
Stressing cancer cells with phenformin
The drug phenformin is a chemical cousin to the diabetes drug metformin, used by more than 120 million people worldwide. Phenformin is 50 times stronger than metformin. Doctors withdrew phenformin from clinical use in the 1970s because some patients experienced a buildup in lactic acid.
Shackelford and his team found that phenformin induced what he calls “lethal energetic stress” in lung cancer cells by poisoning the machinery in the cancer cells that generates energy.
The drug worked by hijacking normal processes within the cell. In normal cell function:
- Exercising depletes stores of ATP, the cell’s fuel.
- In response, cells activate pathways that sense energy stress.
- Cells begin to shut down active growth to free up energy.