Endoxifen is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptor that also inhibitsaromatase activity.
The estrogen receptor (ER) is not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with antiestrogens[4]. Endoxifen is a potent antiestrogen that functions in part by targeting ERα for degradation by the proteasome in breast cancer cells[5]. Treatment of B16F10 mouse and SK-MEL-5 human melanoma cell lines with 10 μM of endoxifen for 48 h respectively resulted in 93.6 and 92.5% cell death. Orally administered endoxifen, at dose levels of 4 and 8 mg/kg body weight/day for 20 consecutive days, respectively reduced metastatic melanoma nodules in the lungs of B16F10 cell-bearing C57BL/6 mice by 26.7 and 82.7%[6]. Oral endoxifen administration once a day for 28 consecutive days at dosages 2, 4, and 8 mg/kg proved safe and resulted in progressive inhibition of the growth of the human mammary tumor xenografts in female mice making endoxifen a potentially new therapeutic agent for breast cancer[7].
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