Drug Targeting Fat Synthesis In Cancer Cells Slows Tumor Growth

To support their rapid growth and proliferation, cancer cells rely on an increased rate of fat synthesis. Researchers at the Salk Institute in La Jolla, California have exploited this requirement by using fat synthesis as a drug target to slow tumor growth, while preserving surrounding healthy tissue.

All cells must synthesize their own fat molecules to support the construction of plasma membranes and other cellular structures, however cancer cells accelerate this process to maintain the rapid growth of tumors. The researchers published their findings in the journal, Nature Medicine.

“Cancer cells rewire their metabolism to support their rapid division,” said Dr. Reuben Shaw, William R. Brody Chair at the Salk Institute, and senior author on the publication. Since Shaw’s team and other researchers have identified a link between fat metabolism and cancer, they sought out to determine whether fat synthesis blocking drugs could be useful anticancer agents.

In partnership with Nimbus Therapeutics, a biotech company based in Boston which focuses on small molecule drug discovery, the team tested a drug candidate in animal models of cancer. The drug – an acetyl-coA carboxylase (ACC) inhibitor called ND-646 – blocks the ACC enzyme which is important in fat synthesis.

Compared to untreated animals with cancer, the ACC inhibitor drug was able to shrink tumor size by over 60 percent. When combined with the DNA damaging drug carboplatin, an effective treatment for non-small cell lung cancer, the power of the experimental inhibitor was boosted.

When combined with ND-646, carboplatin suppressed 87 percent of tumors, compared to only 50 percent when carboplatin was administered on its own. Despite the drug combinations power to significantly slow tumor growth, the researchers say they had no negative impact on healthy cells.

According to Shaw, the study is the first to show that ACC is integral to tumor growth. Along with identifying fat synthesis as a powerful drug target, the team believes they have a “very promising drug” in ND-646, which could be tested in future clinical trials.