Abstract 5847: A histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth with apoptosis in triple-negative breast cancer cells

Abstract

Abstract Purpose: Triple negative breast cancer (TNBC) is the most aggressive subtype in breast cancer. Eribulin is one of the well-tolerated chemotherapeutic drugs for the treatment of metastatic breast cancer. We usually administer eribulin or eribulin with anti-HER2 antibodies. Eribulin was approved for metastatic breast cancer refractory to anthracyclins and taxanes through EMBRACE trial, and the subgroup analysis indicated the efficacy of eribulin was effective in patients with TNBC. However, the prognosis of patients with TNBC is still poor because of the various molecular characteristics. Therefore, there is an urgent need for more effective treatment for the management of TNBC. Methods: We investigated the effect of eribulin in several TNBC cell lines. Eribulin inhibited the cell growth of TNBC cells in a dose-dependent manner. However, eribulin increased the expression of survivin, known to inhibit apoptosis. To counteract the up-regulation of survivin by eribulin, we used OBP-801, a novel histone deacetylase (HDAC) inhibitor, because HDAC inhibitors were reported to suppress the expression of survivin. Results: Co-administration of OBP-801 with eribulin showed a synergistic inhibition of cell growth in TNBC cells. The mechanism of this combination is due to the enhancement of apoptosis. The apoptosis was partially dependent on caspase, and it was via the suppression of not only survivin as expected, but also Bcl-xL. OBP-801 could suppress the survivin expression induced by eribulin at both protein and mRNA level. Interestingly, the combination more potently suppressed a MAPK pathway than each agent. Conclusion: We found that the combination of eribulin and OBP-801 synergistically inhibits the growth with apoptosis in TNBC cells, raising the possibility that the combination might be a novel promising strategy against TNBC patients. Citation Format: Hisako Ono, Yoshihiro Sowa, Yosuke Iizumi, Mano Horinaka, Tetsuya Taguchi, Toshiyuki Sakai. A histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth with apoptosis in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5847.