Much of research to beat cancer tends to concentrate on the various genetic mutations behind different cancers. Now, a new study in the journal Cancer Cell takes a different approach – it targets the pathways that hungry cancer cells use to satisfy their voracious appetite for energy.
Cancer cells grow fast and divide, and to do this they rely on preferred ways of getting energy – even if other means are available.
The idea of foiling cancer by undermining the way it uses energy differently to healthy cells is not new, but it has received more attention lately.
For their study, researchers at Saint Louis University, MO, focused on two metabolic pathways that senior author Thomas Burris, professor and chair of pharmacology and physiology, says cancer cells are “addicted to.”
“They need tools to grow fast,” explains Prof. Burris, “and that means they need to have all of the parts for new cells and they need new energy.”
One pathway that cancer cells use to make the parts they need, is called the Warburg effect, which ramps up use of glucose, and the other is called lipogenesis, whereby the cells can make their own fats for rapid growth.
SR9243 shuts off cancer cells’ preferred fat and sugar energy sources
In their study paper, the team explains how a small molecule that selectively targets these two pathways stopped cancer cell growth in cultured tumor cells in the lab and in human tumor cells grown in animals without harming healthy tissue or inducing weight loss, inflammation or liver damage.
The small molecule – called SR9243 – started off as an anticholesterol drug candidate. The drug targets fat synthesis in cells so they can’t produce their own fat. It also suppresses abnormal glucose consumption and cuts off cancer cells’ energy supply.
The molecule stops these two processes by turning down the genes that drive them. Denied their favorite fat and sugar energy sources, the cancer cells cannot make the parts they need to thrive and die.
The researchers say that because the Warburg effect is not a feature of normal cells and because most normal cells can get their fat from outside, SR9243 only kills cancer cells and does not harm healthy cells.
Prof. Burris explains that some cancers are more sensitive to the drug than others: “It worked very well on lung, prostate and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers.”
The team found SR9243 also seems to work on glioblastoma, a type of brain cancer that is very hard to treat. However, the drug is not able to cross the blood-brain barrier very effectively, so the challenge will be to find a way to help it to do that.
It also appears that SR9243 can increase the effectiveness of existing chemotherapy drugs when used in combination with them.
Meanwhile, Medical News Today recently learned how correcting disruption to a tumor suppressor gene in mice successfully reverted colorectal cancer cells to normal functioning cells. Within 2 weeks, the tumors regressed and disappeared, or reintegrated into normal tissue, say researchers writing in the journal Cell.
Written by Catharine Paddock PhD