Based on data generated using bioinformatics, two drugs approved by the U.S. Food and Drug Administration (FDA) to treat symptoms of depression were tested on SCLC cells and animal models.
Both antidepressants were found to induce SCLC cell death. They were also effective in mice bearing human SCLCs that had become resistant to the chemotherapy drug cisplatin.
The antidepressants tested were imipramine, which modulates the activity of certain hormones causing mood disorders; and promethazine, a sedative, antiemetic, and antipsychotic drug.
Julien Sage, associate professor of pediatrics and genetics at Stanford University School of Medicine in California, said that they implemented a bioinformatics-based drug repositioning approach toward accelerated evaluation of FDA-approved drugs for cancer treatment.
Sage and colleagues shortlisted six antidepressants, out of which imipramine and promethazine emerged as successful candidates for further study based on the results of experiments using SCLC cell lines and mice bearing human SCLC tumors.
The researchers then generated mutant mice bearing cisplatin-resistant SCLC tumors and found that the growth of chemotherapy-resistant tumors were inhibited by imipramine, suggesting that the identified antidepressants will be effective against SCLCs in patients who developed resistance to standard chemotherapy.
They conducted further experiments and found these two drugs acted on SCLCs primarily by inducing cell death mechanisms within the cancer cells. They also found that SCLC cells express certain receptors called GPCRs, and imipramine and promethazine caused cell death by engaging these receptors and their downstream signaling mechanisms.
The study has been published in Cancer Discovery, a journal of the American Association for Cancer Research.
--ANI (Posted on 28-09-2013)