This novel nuclear action of FTY720-P provides a new mechanism to explain the cytotoxic effects of FTY720 in cell culture and its preclinical antitumor efficacy in many xenograft and syngeneic cancer models.43 Moreover, similar to other HDAC inhibitors, treatment with FTY720 enhances histone acetylation at the ERα promoter leading to its re-expression, and sensitizes ER-negative breast cancer cells to TAM therapy. This evidence concerns the gene ESR1 and cancer.