Researchers have discovered a class of FDA-approved antidepressants that may prove effective in treating patients with small-cell lung cancer – one of the deadliest forms of the disease.
Small-cell lung cancer (SLC) comprises 15 percent of all lung cancers and has a particularly grim prognosis rate.
“SLC is a bad cancer to have,” Dr. Atul Butte, the study’s lead author of the Stanford University School of Medicine. “The five-year survival is only 5 to 6 percent, and most people present with extensive stage cancer.”
The disease is a form of cancer known as neuroendocrine cancer – the same type of cancer that Steve Jobs was diagnosed with – for which few targeted treatments are available.
Rather than developing new drugs to treat diseases like SLC, Butte and his colleagues have long been interested in the concept of identifying already FDA-approved drugs that might be repurposed to treat new disorders. With this purpose in mind, Butte’s laboratory developed a computer algorithm able to identify drugs that target genes associated with certain diseases – and match them with one another.
“Basically, a report in the past called for drugs,” Butte said.
Using this computerized discovery pipeline, the researchers began to explore whether any existing drugs might prove effective at killing SLC cells.
“What we started with was looking at experiments where people submitted normal tissue and SLC tissue from the same patients,” Butte said. “We (identify) the gene that is most different in the cancerous cells and then find a drug to reverse that effect.”
Eventually, researchers hit upon a drug called imipramine, which is part of a class of FDA-approved drugs known as tricyclic antidepressants. When researchers exposed SLC-infected tissues to imipramine, the cancerous cells appeared to die off. Researchers tested the drug with success in both a lab setting and using mice genetically engineered to develop small-cell lung cancer.
While tricyclic antidepressants are still on the market, they’ve been overshadowed by the popularity of newer classes of antidepressants, including selective-serotonin reuptake inhibitors (SSRIs), like Prozac, which have been proven to have fewer side effects.
“But not so long ago (tricyclic antidepressants) were commonly used,” Butte said. “They do have side effects, the biggest is on the heart, like arrhythmia… that being said these drugs are still in the pharmacy and you can get them.”
Because these drugs are already FDA-approved, researchers were able to start recruiting patients for phase 2 clinical trials within 15 to 20 months of their discovery.
“Usually it takes $4 billion and 10 plus years to get a brand new drug to market,” Butte said. “This could be a shortcut – finding a drug that works and borrowing it for other disease. We don’t know yet if the trial will work or not but its amazing it will get to trial so quickly.”
However, Butte warns that just because the drug is already on the market, doesn’t mean that patients should attempt to self-medicate.
“We would strongly encourage them to join a trial and get this kind of medication in a research setting, making sure they’re following safety guidelines for this category,” Butte said.