Accession Number : ADA613784


Title :   Development of Antidepressants as Novel Agents To Treat Small Cell Lung Cancer


Descriptive Note : Annual rept. 1 Aug 2013-31 Jul 2014


Corporate Author : STANFORD UNIV CA


Personal Author(s) : Sage, Julien


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a613784.pdf


Report Date : Aug 2014


Pagination or Media Count : 24


Abstract : 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 chemona ve and chemoresistant SCLC cells. 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. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.


Descriptors :   *ANTIDEPRESSANTS , *LUNG CANCER , ACTIVATION , APOPTOSIS , GENE EXPRESSION , NEOPLASMS , PROTEINS , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE