Monday, October 7, 2013

New class of antidepressants appears potentially effective in combating deadly form of lung cancer

Jahchan tested the effect of a tricyclic antidepressant called imipramine  (see structure)  on human small-cell lung cancer cells grown in the laboratory and growing as tumors in laboratory mice. She found that the drug was able to potently activate a self-destruction pathway in the cancer cells and to slow or block metastases in the animals. The drug maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments. Another drug, an antihistamine called promethazine, identified by the bioinformatics screen, also exhibited cancer-cell-killing abilities.

Although imipramine did not affect cells from another main type of lung cancer called non-small-cell lung adenocarcinoma, it did inhibit the growth of cells from other neuroendocrine tumors, including pancreatic neuroendocrine cancers, an aggressive skin cancer called Merkel cell carcinoma, and a pediatric cancer called neuroblastoma. (Neuroendocrine cells receive signals from the nervous system and secrete hormoneslike adrenaline into the blood to affect the body's function.)

Further investigation showed that the drugs appear to work through a class of molecule on the cancer cells' surfaces called G-protein-coupled receptors, but the researchers are continuing to investigate exactly how the drugs specifically kill neuroendocrine cancer cells.
"Our collaboration with the Butte lab allowed us to move very quickly from the initial idea to very convincing results," Sage said. "It was less than 20 months from the time of our first discussion to a clinical trial because the bioinformatics approach had been established and the drugs are FDA-approved. By focusing on diseases with little hope for the patient, it's easier to go forward fast."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2013/09/16/2159-8290.CD-13-0183.abstract

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