Two drugs that are currently approved to treat symptoms of depression may also be effective against small cell lung cancer (SCLC). Researchers used bioinformatics, which combines mathematics and computer science to analyze large amounts of biological data, to pinpoint drugs likely to act on pathways that are important in SCLC. They identified the antidepressant imipramine (Tofranil) and the sedative/anti-nausea medication promethazine (Phenergan). Both drugs killed SCLC cells both in cell culture and in mouse models of chemotherapy-resistant SCLC. SCLC tumors arise from cells that are part of the hormone and nervous system, which may explain the effectiveness of these drugs. A new clinical trial will explore the effectiveness of desipramine (Norpramin), a drug similar to Tofranil, in SCLC.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)–approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein–coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma.