Accession Number:

AD1016343

Title:

Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer

Descriptive Note:

Technical Report,01 Aug 2013,31 Jul 2015

Corporate Author:

Leland Stanford Junior University Stanford United States

Personal Author(s):

• Sage,Julien

Report Date:

2015-10-01

Pagination or Media Count:

15.0

Abstract:

Small cell lung cancer SCLC is an aggressive neuroendocrine subtype of lung cancer withhigh mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and DrugAdministration FDA-approved drugs to treat SCLC. We found that tricyclic antidepressantsand related molecules potently induce apoptosis in both chemonave and chemoresistant SCLC cells. The candidate drugs activate stress pathways and induce cell death in SCLC cells, atleast in part by disrupting autocrine survival signals involving neurotransmitters and theirG protein-coupled receptors. These experiments identify novel targeted strategies that can berapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.

Descriptors:

• lung cancer
• antidepressants
• therapy
• cell physiological processes
• clinical trials
• stem cells
• gene expression
• neoplasms
• computational biology
• chemotherapy

Subject Categories:

Distribution Statement:

APPROVED FOR PUBLIC RELEASE