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Scientists develop new drug to combat tamoxifen-resistant tumors.(Brief Article)
2002 APR 11 - (NewsRx.com & NewsRx.net) -- An antiestrogen compound discovered only 4 years ago, has been found to inhibit the growth of breast cancer cells using a unique mechanism which enables it to work against tumors that are resistant to other antiestrogens, the 3rd European Breast Cancer Conference in Barcelona (March 2002).
Yasuji Yamamoto, from the Institute of Molecular and Cellular Biosciences at the University of Tokyo in Japan, said the compound, known as TAS-108, was being assessed in phase I clinical trials at the M.D. Anderson Cancer Center, Houston, Texas.
"We believe that TAS-108 is a promising antiestrogen for the treatment of breast cancer patients," said Dr. Tetsuji Asao, product director of Taiho Pharmaceutical Co., Ltd., the company that developed TAS-108. "In particular, it appears to inhibit the growth of tamoxifen-resistant tumors. We plan to confirm its efficacy in breast cancer patients who have become resistant to tamoxifen and/or aromatase inhibitors by clinical phase II and III trials. We would welcome collaborating in clinical trials with a partner in the States and Europe."
TAS-108 is a steroidal antiestrogen which was discovered in 1998 by scientists at two institutions: SRI International in California, and Taiho, based in Tokyo, Japan. As well as inhibiting the growth of estrogen-dependent breast tumors it also appears to exert a protective effect on the skeleton and the cardiovascular system. Since its discovery Mr. Yamamoto and colleagues have been investigating how the compound works at the molecular level.
They compared TAS-108 with other leading antiestrogens: tamoxifen, raloxifene and faslodex. They found that only faslodex matched TAS-108 in its ability to inhibit the activities of the estrogen receptors on the tumor cells, while tamoxifen and raloxifene were only partially successful. In addition, TAS-108 and faslodex were both able to overcome tamoxifen resistance caused by a mutated estrogen receptor, ERaD351Y. However TAS-108 differed from faslodex in one crucial area which made it far more effective than any of the other antiestrogens. Yamamoto discovered that it recruited another molecular signal, a corepressor, to help it inhibit the activities of the estrogen receptors. The corepressor, SMRT ...
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