Abstract 5314: Selinexor, a selective inhibitor of nuclear export (SINE) compound, enhances the anti-tumor activity of Eribulin in leiomyosarcoma

Abstract

Abstract Leiomyosarcoma (LMS) is a rare soft tissue sarcoma (STS) that begins in smooth muscle tissue and most often initiates in the abdomen or uterus. Compared with other uterine cancers, uterine LMS is an aggressive tumor associated with poor prognosis and has a high risk of recurrence and death, regardless of stage at presentation. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) compound that binds covalently to exportin 1, thereby reactivating tumor suppressor proteins and downregulating the expression of oncogenes and DNA damage repair (DDR) proteins. Selinexor has demonstrated preclinical activity in various cancer types, including STS, and is currently in Phase I and II clinical trials for advanced cancers (Marretta et al. 2021). In this study, we evaluated the effects of Selinexor in combination with Dacarbazine, Gemcitabine, Doxorubicin, Pazopanib, Eribulin, and Trabectedin in LMS cell lines. The effects on cell viability were evaluated by treating the LMS cell lines SK-UT1 (p53-mut) and SK-UT1-B (p53 WT) with Selinexor and different chemotherapy combinations. Treatment with these drugs significantly decreased the cell proliferation and survival of SK-UT1 and SK-UT1-B cell lines tested in vitro. However, this effect was enhanced in SK-UT1 cells following treatment in the combination of Selinexor with Eribulin and Doxorubicin. The effects of treatment were also evaluated in mouse xenograft models generated with SK-UT1 cell lines. Treatment with Selinexor combined with Eribulin showed synergistic effects on tumor growth inhibition in SK-UT1 derived xenografts which warrant further investigation of these combinations at the clinical level. Citation Format: Sonam Mittal, Ishaque Pulikkal, Hua Chang, Yosef Landesman, John Charlson, Sunila Pradeep. Selinexor, a selective inhibitor of nuclear export (SINE) compound, enhances the anti-tumor activity of Eribulin in leiomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5314.