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Using Repurposed Antidepressants to Treat Lung Cancer

Imipramine and promethazine may help lung cancer patients (September 26)

Researchers at Stanford have identified a class of antidepressants as a potential new therapy for small-cell lung cancer (SCLC), according to a study published in Cancer Discovery.

Based on data generated using bioinformatics, two FDA-approved antidepressants were tested on SCLC cells and animal models. The antidepressants tested were imipramine, which modulates the activity of certain hormones causing mood disorders, and promethazine, a sedative, antiemetic, and antipsychotic drug. Both drugs induced SCLC cell death and were effective in mice bearing human SCLCs that had become resistant to cisplatin, a chemotherapy drug.

Unlike most targeted therapies, which are often specific for a single molecule or pathway, the drugs used in this study identified target multiple receptors at the surface of neuroendocrine cancer cells, which may make it difficult for cancer cells to develop resistance. The investigators are in the process of identifying the optimal regimen for patients with SCLC and modifying these drugs to prevent them from entering the brain in order to minimize side effects.

SCLC is a deadly subtype of lung cancer of neuroendocrine origin. There is no approved targeted therapy for this disease, and no new drugs have been identified in the last few decades.

The investigators focused their search on drugs that targeted the two top pathways identified using a bioinformatics approach: the neuroactive ligand receptor interaction pathway and the calcium-signaling pathway. In mutant mice bearing cisplatin-resistant SCLC tumors, the growth of chemotherapy-resistant tumors was inhibited by imipramine.

The researchers have initiated a Phase IIA trial to test desipramine, which is similar to imipramine, in SCLC and other high-grade neuroendocrine tumors. The intellectual property from this work has been licensed to NuMedii, a company planning further study.

[ Source: Cancer Discov; 2013;3(12);1–14, September 26, 2103. © American Association for Cancer Research.]

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