Bioinformatics Approach IDs Approved Drugs for Repurposing
Approach found that tricyclic antidepressants may be effective for small cell lung cancer
FRIDAY, Sept. 27 (HealthDay News) -- Bioinformatics-based drug approaches have identified U.S. Food and Drug Administration-approved drugs and a novel class of molecules that can be repurposed to treat patients with small cell lung cancer (SCLC), according to research published online Sept. 26 in Cancer Discovery.
Nadine S. Jahchan, Ph.D., from Stanford University in California, and colleagues used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate FDA-approved drugs to treat SCLC.
The researchers found that tricyclic antidepressants and related molecules potently induced apoptosis in both chemonaive 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. Stress pathways were activated by the candidate drugs to induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. Growth of other neuroendocrine tumors was inhibited by the candidate drugs, including pancreatic neuroendocrine tumors and Merkel cell carcinoma.
"These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs," the authors write.
Several authors disclosed financial ties to NuMedii, the developer of these drugs, and are named on patents for the use of specific tricyclic antidepressants in neuroendocrine tumors.
Abstract (http://cancerdiscovery.aacrjournals.org/content/early/2013/09/16/2159-8290.CD-13-0183.abstract )Full Text (subscription or payment may be required) (http://cancerdiscovery.aacrjournals.org/content/early/2013/09/16/2159-8290.CD-13-0183.full.pdf+html )