Stanford scope blog: researchers discovered that fluoxetine (a common antidepressant commonly known as Prozac) appears to target a difficult to treat, often deadly brain cancer called glioblastoma The brain's unique make up is part of what makes these cancers difficult to treat. It's sequestered from the rest of the body by the blood-brain barrier, which protects precious nerve cells from potential bad agents circulating in the blood stream.
But this barrier also prohibits the entry of many medications -- another hurdle to overcome when designing drugs to target brain cancers. Finally, glioblastomas are known to have many copies of cancer-associated genes, including one called the epidermal growth factor receptor, or EGFR.
"In most cancers, EGFR is mutated to become more active, but in glioblastomas the EGFR gene is instead amplified many times," Mischel said. "But previous work in my lab showed that targeting these amplifications directly wasn't successful."
Mischel and Bi knew that the balance of cholesterol and a class of fats called lipids is often severely disrupted in glioblastoma cells. They also knew that these lipids are important in EGFR signaling. After a series of deductions, they homed in on a lipid called sphingolipid as potentially important in glioblastoma growth and survival.
They found that people with glioblastomas whose cancers made high levels of an enzyme involved in sphingolipid metabolism called SMPD1 had significantly shorter lifespans than patients whose cancers expressed lower levels of the enzyme.”