Lethal Energetic Stress

Tumors, however, don’t have the ability to control their growth in this way. Instead, they grow too fast, overstress themselves and die. “As cancer advances, the cells lose their braking mechanism,” Shackelford says.

Having found this tantalizing Achilles heel, Shackelford and his team started to examine the way cancer metabolizes other nutrients. Now, they are continuing to seek ways to take advantage of the crash caused by brake failure.

This phenomenon is similar to what Thomas Graeber, PhD, describes, but in this case, a drug causes it. Read more about Graeber’s work with metabolism and biochemical signaling.

Using PET and novel biomarkers, the researchers examined the effect of withholding nutrients from tumors. While most researchers do studies like this using pulverized tissue, the UCLA team uses non-invasive PET scans to see the effect of different therapies in real time.

They tested metabolic pathways one by one. Without glucose, many tumors could not grow, but some could.

The group then looked at cancer’s use of glutamine, an essential amino acid that is part of the cell’s food supply. They found that a subset of very aggressive lung tumors switch from using glucose to using glutamine and other amino acids for growth.

As this work develops, researchers are finding new ways to study tumor changes.

Ultimately, doctors won't have to wait for months to see if therapies work, as they do now. Instead, doctors will be able to treat tumors metabolically.

In the future, doctors may adopt these findings for clinical care. In that process, physicians could:

• Test tumors in a cancer patient for their use of glucose
• Choose a targeted therapy
• Scan the tumors for their preferred amino acid
• Choose another therapy if needed
• Continue scanning and testing, as needed, through the list of nutrients and associated therapies that induce energetic stress

This new era continues with additional investigations into:

• Slowing glucose metabolism: Researchers are currently conducting phase 1 and 2 clinical trials of a compoundat slows glucose metabolism. Heather Christofk, PhD, played a major role in designing the compound. These studies are being held outside of UCLA, with the help of a company that Christofk helped start.
• Targeting amino acids: Other researchers are testing a molecule that Schackelford investigated that targets use of amino acids for fuel in lung, kidney and triple negative breast cancers.

Learn About Cancer Research At UCLA