DNAH8 and breast cancer: These results are consistent with published preclinical data showing that 4-OH-tamoxifen (the active metabolite of tamoxifen) may act as a HSP90 activator by stimulating its ATPase activity [46], and that modest HSP90 inhibition, below the threshold for proteotoxic activation of the heat shock response, dramatically impairs the emergence of tamoxifen resistance in cell culture and mouse models of breast cancer [47], raising the interesting hypothesis that an intact HSP90 activity is indeed necessary to take full advantage of tamoxifen-based combinations in this context.