Researchers at Saint Louis University, in Missouri, focused on two metabolic pathways to which senior author Thomas Burris, professor and chair of pharmacology and physiology, says cancer cells are "addicted." According to Prof. Burris, "They need tools to grow fast, and that means they need to have all of the parts for new cells and they need new energy." Cancer cells use two pathways to make the parts they require -- the Warburg effect, which speeds up the use of glucose, and lipogenesis, which gives the cells a way to make their own fats for rapid growth.
According to the Medical Dictionary (http://medicaldictionary.thefreedictionary.com), the Warburg effect is the observation, first made by Otto Heinrich Warburg, that most malignantcells obtain their energy from anaerobic metabolism, at rates of glycosis of as much as 200 times greater than oxidative metabolism of pyruvate in mitochondria. This effect caused Warburg to conclude that the fundamental change in cancer was metabolic, rather than genetic. According to the same source, lipogenesis is the formation of fatty acids from carbohydrate, mainly in the liver, after which fatty acids can be formed from carbohydrates and then combined with triglycerol to form triglycerides.
The research team explained how a small molecule, called SR9243, 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." SR9243 started as an anticholesterol drug candidate. It targets fat synthesis in cells to keep them from producing their own fat, suppresses abnormal glucose consumption and cuts off the energy supply of cancer cells. By turning down the genes that drive these processes, the drug stops them. When cancer cells are cut off from their favorite energy sources, they cannot make the parts they need to thrive. Thus, they die. However, "because the Warburg effect is not a feature of normal cells and because most normal cells can get their fat from outside," the drug only kills cancer cells and does not harm healthy cells.
According to Prof. Burris, some cancers are more sensitive to the drug than others. He said that SR9243 "worked very well on lung, prostate and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers." While it also seems to work on glioblastoma, a type of brain cancer that is very hard to treat, it is not able to cross the blood-brain barrier very effectively. The team is trying to find a way to help it to do that. SR9243 may also increase the effectiveness of existing chemotherapy drugs when used in tandem with them.