Tumors have a voracious appetite for fat and rely on hastened fat synthesis in cancer cells to satisfy their need. Now, a new study shows it is possible to use drugs to shut down fat synthesis in cancer cells to stunt tumor growth without harming healthy cells.
The researchers found cells treated with a placebo produced more fat (red, on left) than cells treated with the enzyme inhibitor (right).
Image credit: Salk Institute
A report on the study is published in the journal Nature Medicine.
The discovery – by researchers at the Salk Institute in La Jolla, CA, and collaborators – represents a new frontier in the search for targeted treatments against cancer, a leading cause of disease and premature death worldwide.
The new research centers around the fact that cells synthesize their own fat molecules – an essential building material for plasma membranes and other important structures.
Cancer cells speed up this process to fuel the abnormally rapid growth of tumors, as Prof. Reuben Shaw, who heads the Salk team, explains:
“Cancer cells rewire their metabolism to support their rapid division.”
Prof. Shaw and the researchers in his lab have made considerable headway in linking cancer and metabolic processes. Others have previously suggested cancer cells appear to be more reliant on fat synthesis than normal cells. The team also noticed this and wondered whether this might make cancer cells more sensitive to drugs that block or reduce the process.
Small molecule shuts off key fat synthesis enzyme
For the study, the Salk researchers teamed up with Nimbus Therapeutics, a Boston-based biotech that specializes in discovering small molecule drugs.
Fast facts about cancer
- New cases of cancer are expected to rise by about 70 percent over the next 20 years
- Tobacco use, alcohol use, unhealthy diet, and physical inactivity are the main risk factors for cancer worldwide
- Nearly a third of cancer deaths could be prevented by modifying or avoiding these and other risk factors.
Learn more about cancer
Nimbus were already investigating a small molecule that shuts off an enzyme called Acetyl-CoA Carboxylase (ACC) that is important for fat synthesis in cells.
The collaborators tested the new ACC inhibitor – called ND-646 – in several large-scale experiments in both animal models of cancer and in transplanted cancer cells.
The results were better than they expected. Tumors shrank by around two thirds, compared with untreated animals, they note.
They also found that when given with carboplatin, a common treatment for non-small lung cancer (NSLC), the effect was even more powerful.
Carboplatin works by damaging DNA, which causes problems for rapidly dividing cells.
The results showed that ND-646 with carboplatin suppressed 87 percent of tumors, compared with 50 percent when carboplatin is given on its own.
The combination did not seem to impair healthy cells – even as it dramatically slowed tumor growth, note the researchers.
‘Very promising drug’ for clinical trials
Prof. Shaw says the study is the first time anyone has demonstrated that ACC is essential for tumor growth. It provides “compelling data” to validate the idea that targeting fat synthesis could be a new way to fight cancer.
He says they now have a “very promising drug” for clinical trials for subtypes of lung cancer, and also liver and other types.
According to the World Health Organization (WHO), around 14 million new cases arose and 8.2 million people died of cancer-related causes in 2012 (the most recent year for global data).
In that year, the lung, prostate, colorectum, stomach, and liver were the most common sites for cancer diagnosis in men. For women, they were breast, colorectum, lung, cervix, and stomach.
“This represents a new weapon in the arsenal to fight cancer.”
Prof. Reuben Shaw
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