Swaathi Jayaraman, Xinyan Wu, Krishna R Kalari, Xiaojia Tang, Mary J Kuffel, Elizabeth S Bruinsma, Shahrzad Jalali, Kevin L Peterson, Cristina Correia, Rachel A Kudgus, Scott H Kaufmann, Santosh Renuse, James N Ingle, Joel M Reid, Matthew M Ames, Alan P Fields, Matthew J Schellenberg, John R Hawse, Akhilesh Pandey, Matthew P Goetz
Endoxifen, a secondary tamoxifen metabolite, is a potent antiestrogen exhibiting estrogen receptor alpha (ERα) binding at nanomolar concentrations. Phase I/II clinical trials identified clinical activity of Z-endoxifen (ENDX), in endocrine-refractory metastatic breast cancer as well as ERα+ solid tumors, raising the possibility that ENDX may have a second, ERα-independent, mechanism of action. An unbiased mass spectrometry approach revealed that ENDX concentrations achieved clinically with direct ENDX administration (5 µM), but not low concentrations observed during tamoxifen treatment (<0...
December 19, 2023: NPJ Breast Cancer