Scientists have for the first time found a way to stop cancer cell growth by targeting a trait of cancer cell metabolism: its energy source.
Unlike recent advances in personalised medicine that focus on specific genetic mutations associated with different types of cancer, this research targets its energy source - a broad principle that applies to almost every kind of cancer.
The study, which was conducted in animal models and in human tumour cells in the lab, showed that a drug developed by researchers can stop cancer cells without causing damage to healthy cells or leading to other severe side effects.
Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. This preference is called the Warburg effect, or glycolysis.
"Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don't have the parts, they just die," said Thomas Burris, from Saint Louis University.
"The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow," said Burris.
Burris and colleagues at Scripps Research Institute hypothesised targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers.
Researchers created a class of compounds that affect a receptor that regulates fat synthesis. The compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can't produce their own fat.
This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells' energy supply.
When cancer cells don't get the parts they need to reproduce through glucose or fat, they simply die.
Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells, researchers said.
The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation.
So far, SR9243 has been tested in cultured cancer cells and in human tumour cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models.
"Some are more sensitive to it than others. In several of these pathways, cells had been reprogrammed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells," said Burris.
In human tumours grown in animal models, Burris said, "it worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers."
It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer.
The research was published in the journal Cancer Cell.
