An older and little-used class of antidepressants may be an effective weapon in the battle against small cell lung cancer (SLC), according to a new study published online in the Sept. 26 journal Cancer Discovery.
Small cell cancers account for only 15 percent of all lung cancers, but they are particularly deadly.
“The five-year survival for small cell lung cancer is only 5 percent,” senior study co-author Julien Sage, PhD, an associate professor of pediatrics at Stanford School of Medicine, said in a 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,” said Sage.
Specifically, the drugs activated a cellular self-destruct pathway that killed the cancer cells.
The Stanford researchers used a unique computer program to identify tricyclic antidepressants – approved by the Food and Drug Administration (FDA) since the 1950s but seldom used today – as a potential treatment for small cell lung cancer.
“What we started with was looking at experiments where people submitted normal tissue and SLC tissue from the same patients. We [identified] the gene that is most different in the cancerous cell and then a drug to reverse the effect,” senior co-senior study author Atul Butte, MD, PhD, division chief of systems medicine and director of the Center for Pediatric Bioinformatics at Lucile Packard Children’s Hospital at Stanford, told Fox News.
Follow-up research showed that a particular antidepressant, imipramine (Tofranil), was effective against human SCL cells grown in the lab and grown as tumors in lab mice. The drug maintained its effectiveness regardless of whether the cancer cells had been exposed, and became resistant to, traditional chemotherapy treatments.
What makes this discovery especially significant is that it involves a drug that has already been approved by the FDA, allowing the Stanford research team to quickly launch a phase-2 clinical trial to test imipramine in patients with SCL and other types of cancer.
“We are cutting down on 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 or two years and spending about $100,000,” said Butte in the news release.
Because of side-effects that include increased heart rate, tremors, confusion and seizures, study authors warn patients against using the tricyclic antidepressants on their own. Rather, they encourage them to join a trial and get the medication in a setting that ensures safety guidelines are being followed.
Information about the phase-2 clinical trial can be found at ClinicalTrials.gov.