An older and little-used class of antidepressants may help combat a particularly deadly form of lung cancer, according to a new study.
Using a unique computer program, researchers from the Stanford University School of Medicine identified tricyclic antidepressants as a potential treatment for small cell lung cancer. This class of drugs was introduced decades ago and is still approved for use in the United States, but has been supplanted by newer antidepressants with fewer side effects.
Follow-up experiments showed that the tricyclic antidepressant called imipramine (Tofranil), was effective against human small cell lung cancer cells grown in the laboratory and growing as tumors in mice. The drug activated a self-destruction pathway in the cancer cells and slowed or blocked the spread of cancer in mice.
Imipramine maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments, according to the study, which was published online Sept. 27 in the journal Cancer Discovery.
Because tricyclic antidepressants already have U.S. Food and Drug Administration approval for use in people, the Stanford team was quickly able to launch a clinical trial to test imipramine in patients with small cell lung cancer and certain other types of cancer. They are currently recruiting patients for the phase-2 trial.
"We are cutting down the decade or more and the $1 billion it can typically take to translate a laboratory finding into a successful drug treatment to about one to two years and spending about $100,000," study co-senior author Dr. Atul Butte, director of the Center for Pediatric Bioinformatics at Lucile Packard Children's Hospital at Stanford, said in a university news release.
"The five-year survival for small cell lung cancer is only 5 percent," study co-senior author Julien Sage, an associate professor of pediatrics, said in the news release. "There has not been a single efficient therapy developed in the last 30 years. But when we began to test these drugs in human cancer cells grown in a dish and in a mouse model, they worked, and they worked, and they worked."
Another drug, an antihistamine called promethazine (Phenergan), also exhibited the ability to kill cancer cells, according to the researchers.