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Kidney cancer secrets revealed by Stanford researchers

I enjoyed recently writing about a collaboration among researchers from Stanford's School of Medicine and the School of Humanities and Sciences. Oncologist Dean Felsher, MD, PhD, and chemist Richard Zare, PhD, joined forces to learn more about a kidney cancer called renal cell adenocarcinoma; their research was published in the Proceedings of the National Academy of Sciences earlier this week.

In the future, we hope to use this model to... identify those kidney cancer patients who might respond favorably to specific therapies

Together Felsher and Zare found that an aggressive form of kidney cancer has a distinct lipid profile (lipids are a class of molecules found in cell membranes; they also function in cellular signaling pathways and in energy storage). To do so, they used a new technology called desorption electrospray ionization mass-spectrometric imaging, or DESI-MSI. It sounds complicated, but it led directly to a new, previously unsuspected therapeutic approach that may soon be tested in humans. As I described in my article:

DESI-MSI creates a highly detailed, two-dimensional map of the chemical composition of a tissue sample through a process that can be loosely compared to a specialized car wash. Samples are sprayed with a thin, high-powered stream of liquid droplets that dissolve their outer surface. The resulting back spray, which contains molecules from the surface of the sample, is collected and analyzed by mass spectrometry. By moving the tissue sample around in a two-dimensional plane, it’s possible to make a chemical map of its composition.

The researchers found that the cancerous kidney tissue had a chemical composition distinct from that of healthy tissue. In particular, it had higher-than-normal levels of molecules generated as glutamine is metabolized. Blocking the activity of a protein called glutaminase, which is responsible for metabolizing glutamine, caused the animals’ tumors to grow more slowly when [Myc expression was activated].

To conduct the work, researchers in Felsher's laboratory genetically engineered a strain of mice that could be triggered to express high levels of a cancer-associated protein called Myc in the tubules of their kidneys. These mice quickly developed an aggressive form of kidney cancer when Myc was expressed. Conversely, the kidney tumors shrank significantly when Myc expression was halted. As Felsher told me:

In the future, we hope to use this model to categorize different types of kidney cancer and identify those patients who might respond favorably to specific therapies. In the near term, we can test whether blocking glutamine metabolism is a viable approach for people with Myc-dependent liver cancer.

Previously: Unraveling the secrets of a common cancer-causing gene and Smoking gun or hit-and-run? How oncogenes make good cells go bad

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