Microbiome critical for bone hormone action

PTH (parathyroid hormone) increases calcium levels in the blood and can either drive bone loss or bone formation, depending on how it is produced or Read more

More NMDA but less excitotoxicity? Now possible

Many researchers have wanted to enhance NMDA receptor signals to treat disorders such as schizophrenia. But at the same time, they need to avoid killing neurons with “excitotoxicity”, which comes from excess calcium entering the Read more

Update on pancreatic cancer: images and clinical trial

In 2018, Winship magazine had a feature story on pancreatic cancer. Our team developed an illustration that we hoped could convey the tumors’ complex structure, which contributes to making them difficult to treat. Oncologist Bassel El-Rayes described how the tumors recruit other cells to form a protective shell. "If you look at a tumor from the pancreas, you will see small nests of cells embedded in scar tissue," he says. "The cancer uses this scar Read more

V600E

Melanoma mutation likes fat for fuel

Cancer cells love glucose, the simple sugar the body uses for energy, so a high-fat, low-carb diet should starve them, right?

Where does this idea come from? Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect, after 1931 Nobel Prize winner Otto Warburg.

Resurgent interest in exploiting the Warburg effect was described by Sam Apple in NYT Magazine and by Bret Stetka for NPR. High-fat, low-carb “ketogenic” diets are known to be effective against some types of epilepsy, and have also been explored by endurance athletes. Ketogenic diets have been tried as a clinical countermeasure against cancer in a limited way, mainly in brain cancer.

Before everybody gets too excited, let’s think about how particular cancer-driving mutations affect cell metabolism, suggests Winship Cancer Institute researcher Jing Chen. His team’s work in mice suggests that cancers with a common melanoma mutation (BRAF V600E) will grow faster in response to a ketogenic diet. In addition, the Winship researchers found that lipid-lowering agents such as statins curb these cancers’ growth, even in the context of a more normal diet.

The results were published on January 12 in Cell Metabolism.

Caveats: the findings cover just one mutation and need to be tested clinically.

Consumers and cancer patients already get a lot of advice about the right diet to fight cancer, but this research points toward an intriguing concept:  a “precision diet,” tailored to an individual patient’s cancer.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Melanoma mutation rewires cell metabolism

A mutation found in most melanomas rewires cancer cells’ metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

The V600E mutation in the gene B-raf is present in most melanomas, in some cases of colon and thyroid cancer, and in the hairy cell form of leukemia. Existing drugs such as vemurafenib target the V600E mutation — the finding points to potential alternatives or possible strategies for countering resistance. It may also explain why the V600E mutation in particular is so common in melanomas.

Researchers led by Jing Chen and Sumin Kang have found that by promoting ketogenesis, the V600E mutation stimulates production of a chemical, acetoacetate, which amplifies the mutation’s growth-promoting effects. (A feedback mechanism! Screech!)

The results were published Thursday, July 2 in Molecular Cell.

More on this paper here.

Posted on by Quinn Eastman in Cancer 1 Comment