Tanespimycin metastatic breast cancer

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  tanespimycin plus trastuzumab has significant anticancer activity in patients with her2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of hsp90 inhibitors is clearly warranted. Tanespimycin binds to and inhibits the cytosolic chaperone functions of heat shock protein 90 (hsp90). Hsp90 maintains the stability and functional shape of many oncogenic signaling proteins the inhibition of hsp90 promotes the proteasomal degradation of oncogenic signaling proteins that may be overexpressed by tumor cells. To determine the progression free survival (pfs) of patients with refractoryresistant metastatic breast cancer when treated with 17-aag. To correlate patients her2neu status with response to 17-aag treatment. Patients receive tanespimycin iv over 1-6 hours on days 1, 4, 8, and 11. Tanespimycin in treating women with refractory locally advanced or metastatic breast cancer the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Tanespimycin plus trastuzumab has significant anticancer activity in patients with her2-positive, metastatic breast cancer previously progressing on trastuzumab. Phase ii trial of the hsp90 inhibitor tanespimycin (tan) trastuzumab (t) in patients (pts) with her2-positive metastatic breast cancer (mbc) abstract 1027 j clin oncol. Tanespimycin is a potent hsp90 inhibitor with an ic 50 5 nm in a cell-free assay when hsp90 is isolated from tumor cells compared to c. It has been suggested that this is due to an activated form of hsp90 in tumor cells. 127 in cell-based experiments, tanespimycin demonstrated an rb-dependent g1 growth arrest in a range of human tumor cell lines. 1027 background tan (17-aag) inhibits hsp90 activity, resulting in degradation of client proteins including the her2 receptor. A phase 1 trial demonstrated clinical activity of t tan in pts with her2 mbc (1 pr 4 mrs in 15 pts with median of 2 prior t-based regimens modi et al, jco 2007). Tan was initially a cremophor-based product a suspension became available and was substituted in. Tanespimycin plus trastuzumab had significant anticancer activity in patients with her2-positive metastatic breast cancer previously progressing on trastuzumab (modi et al.).

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