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A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors

Sunday, October 20, 2013

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Nadine S. Jahchan, Joel T. Dudley, Pawel K. Mazur, Natasha Flores, Dian Yang, Alec Palmerton, Anne-Flore Zmoos, Dedeepya Vaka, Kim Q.T. Tran, Margaret Zhou, Karolina Krasinska, Jonathan W. Riess, Joel W. Neal, Purvesh Khatri, Kwon S. Park, Atul J. Butte and Julien Sage

This study found that tricyclic antidepressants like Imipramine, used to treat major depression and Promethazine used as an antiemetic and antihistaminic, induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture,v and in mouse and human SCLC tumors transplanted into immunocompromised mice. The relevance of this work is based on the power of bioinformatics to find new drugs to treat SCLC. The authors used gene expression microarrays to know how expression levels change in SCLC compared to normal lung cells. They found a gene expression signature for SCLC by using publically available gene expression data from FDA-approved drugs. Tricyclic antidepressants had a similar signature to previous chemotherapy agents, which suggested their ability to antagonize SCLC growth.

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