SEP 23, 2016 02:26 PM PDT

Compound Blocks Fat Synthesis, Chokes Cancer's Fuel Supply

WRITTEN BY: Xuan Pham

Earlier this week, I reported that scientists discovered how some cancers apparently switched off their sweet tooth to burn fat cells instead. Following this discovery, scientists at the Salk Institute found a drug that targets this fat-loving pathway in cancers.
 

Image credit: Pixabay.com

Two of the better-known fat-loving cancer types are prostate cancer and acute myeloid leukemia. Unlike other cancers that prefer sugar over fat, the fat-loving cancers have a penchant for fat as their main source of fuel. Thus, in these cancers, conventional therapies that aim to starve the glucose pathway are ineffective.

In studying cancer’s appetite for fat, Salk Institute researchers found that when the demand is high, cancer cells actually speed up their own fat production. The feedback mechanism is akin to a self-perpetuating supply and demand chain – as the cancer feeds on more fat, it stimulates the cells to make more fat molecules.

"Cancer cells rewire their metabolism to support their rapid division,” noted Reuben Shaw, who heads the Salk team. Knowledge of this feedback pathway naturally pave the way to exploring potential targets that could block fat synthesis, and thereby starve out the cancer cells.

To find possible targets, the Salk team collaborated with Nimbus Therapeutics, a Boston-based biotech that specializes in discovering small molecule drugs. Together, they investigated a molecule known as ND-646, which is an acetyl-CoA Carboxylase (ACC) inhibitor. ACC is an enzyme that’s vital to fat production, and inhibiting this pathway should shut down fat-loving cancer cells.
 


Indeed, experiments in large-scale animal models showed remarkable results – the tumor shrank by nearly two-thirds as compared to the untreated tumors. Furthermore, choking the cancer’s fat supply seemed to work synergistically alongside a common anticancer drug, carboplatin. The combination of the ACC inhibitor and carboplatin suppressed 87 percent of cancer as compared to the 50 percent reduction from carboplatin alone.

"We found surprisingly well-tolerated dosing with some of these novel ACC inhibitors that have broad bioavailability and should not be far away from what would be needed to initiate clinical trials," said Robert Svensson, a Salk research associate and the study’s first author.

"This is the first time anyone has shown that this enzyme, ACC, is required for the growth of tumors and this represents compelling data validating the concept of being able to target fat synthesis as a novel anticancer approach," said Shaw. "The implications are that we have a very promising drug for clinical trials for subtypes of lung cancer as well as liver and other types of cancer. This represents a new weapon in the arsenal to fight cancer."

Additional source: Salk Institute

About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
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