Ethaselen for the Treatment of Thioredoxin Reductase High Expression Advanced Non-small Cell Lung Cancers

Summary

Thioredoxin reductase plays an critical role in lung cancer patients, in vitro study showed that, ethaselen, specific inhibitor of thioredoxin reductase, could inhibit lung cancer cell growth and induce apoptosis. In China, phase 1 clinical trials of ethaselen showed that 1200 mg dose ethaselen could be well tolerated, in pre-clinical study we found that, approximately 50% non-small cell lung cancers harbored high thioredoxin reductase expression(IHC result ++ or +++), phase 1a/b of ethaselen had finished in 2008, the result showed that 1200mg ethaselen per day was safety and tolerated by Chinese malignant tumor patients.In pre-clinical research, our group found that, elevated of thioredoxin reductase activity was associated with the expression of thioredoxin reductase tested by immunohistochemistry, which means high expression of this enzyme may be a favourite predicted factor of ethaselen, the specific inhibitor of thioredoxin reductase.

Timeline

Start

2014-06-01

Primary completion

2020-12-01

Completion

2021-12-01

Publications

• Background Wang L, Yang Z, Fu J, Yin H, Xiong K, Tan Q, Jin H, Li J, Wang T, Tang W, Yin J, Cai G, Liu M, Kehr S, Becker K, Zeng H. Ethaselen: a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent. Free Radic Biol Med. 2012 Mar 1;52(5):898-908. doi: 10.1016/j.freeradbiomed.2011.11.034. Epub 2011 Dec 21.
• Background Wang L, Fu JN, Wang JY, Jin CJ, Ren XY, Tan Q, Li J, Yin HW, Xiong K, Wang TY, Liu XM, Zeng HH. Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy. Anticancer Drugs. 2011 Sep;22(8):732-40. doi: 10.1097/CAD.0b013e32834618bc.
• Background Poerschke RL, Moos PJ. Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction. Biochem Pharmacol. 2011 Jan 15;81(2):211-21. doi: 10.1016/j.bcp.2010.09.024. Epub 2010 Oct 12.
• Background Zhao F, Yan J, Deng S, Lan L, He F, Kuang B, Zeng H. A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five cultured human carcinoma cell lines. Cancer Lett. 2006 May 8;236(1):46-53. doi: 10.1016/j.canlet.2005.05.010. Epub 2005 Jun 27.
• Background Fu JN, Li J, Tan Q, Yin HW, Xiong K, Wang TY, Ren XY, Zeng HH. Thioredoxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest. Invest New Drugs. 2011 Aug;29(4):627-36. doi: 10.1007/s10637-010-9401-y. Epub 2010 Mar 2.
• Background Tan Q, Li J, Yin HW, Wang LH, Tang WC, Zhao F, Liu XM, Zeng HH. Augmented antitumor effects of combination therapy of cisplatin with ethaselen as a novel thioredoxin reductase inhibitor on human A549 cell in vivo. Invest New Drugs. 2010 Jun;28(3):205-15. doi: 10.1007/s10637-009-9235-7. Epub 2009 Mar 7.

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Indications