Targeting Fat May be the Key to Treating Cancer

Shutting off a critical enzyme in lipid synthesis found to stifle tumor growth.

Targeting fat and halting its synthesis in cells was found to stunt tumor growth, which could offer a potential approach to treating cancer, a study published in Nature Medicine indicates.

Cells are able to create their own fat molecules to build their plasma membranes and other important structures; however, new findings show that stifling this process could stop cancer growth.

“Cancer cells rewire their metabolism to support their rapid division,” said researcher Reuben Shaw. “Because cancer cells are more reliant on lipid synthesis activity than normal cells, we thought there might be subsets of cancers sensitive to a drug that could interrupt this vital metabolic process.”

Previously, researchers hypothesized that interrupting the cell lipid assembly line could disable cancer; however, it was only recently that they were able to disrupt the process to test their theory. Researchers teamed up with Nimbus Therapeutics, who were developing a molecule to shut off a critical enzyme in lipid synthesis called Acetyl-CoA Carboxylase (ACC).

“This confirms that shutting down endogenous lipid synthesis could be beneficial in some cancers and that inhibitors of the ACC enzyme represent a feasible way to do it,” said study co-author Rosana Kapeller, chief scientific officer at Nimbus. “We’ve taken a novel computational chemistry approach to designing high-potency allosteric inhibitors of this difficult enzyme, and we are very encouraged by the results.”

There have been multiple and extensive large scale studies in both animal models of cancer, and in transplanted human lung cancer cells with a novel ACC inhibitor called ND-646. The results of the study showed that the tumor mass decreased by roughly two-thirds compared with untreated animals.

When ND-646 was combined carboplatin, a common treatment for non-small cell lung cancer, the anti-tumor response was dramatic with 87% of tumors suppressed compared to 50% with carboplatin alone. The findings proved to be more promising than originally expected.

The combination treatment also appeared to be well-tolerated, and did not seem to impair normal cells, even as the treatment dramatically slowed cancer growth.

“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 first study author Robert Svensson.

The findings indicate this approach shows potential for the treatment of cancer, according to the study.

“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,” Shaw said. “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.”