Drugs and Drug Candidates (May 2023)

Selinexor and Other Selective Inhibitors of Nuclear Export (SINEs)—A Novel Approach to Target Hematologic Malignancies and Solid Tumors

  • Kajetan Karaszewski,
  • Wiesław Wiktor Jędrzejczak

DOI
https://doi.org/10.3390/ddc2020023
Journal volume & issue
Vol. 2, no. 2
pp. 459 – 476

Abstract

Read online

Exportin 1 (XPO1) is a crucial molecule of nucleocytoplasmic transport. Among others, it exports molecules important for oncogenesis from the nucleus to the cytoplasm. The expression of XPO1 is increased in numerous malignancies, which contributes to the abnormal localization of tumor suppressor proteins in the cytoplasm and subsequent cell cycle dysregulation. Selective inhibitors of nuclear export (SINEs) are novel anticancer agents that target XPO1, arrest tumor suppressor proteins in the nucleus, and induce apoptosis in cancer cells. Selinexor, a first-in-class SINE, has already been approved for the treatment of relapsed/refractory multiple myeloma and relapsed/refractory diffuse large B cell lymphoma not otherwise specified. It has also been proven effective in relapsed/refractory and previously untreated acute myeloid leukemia patients. In addition, numerous studies have yielded promising results in other malignancies of the hematopoietic system and solid tumors. However, future clinical use of selinexor and other SINEs may be hampered by their significant toxicity.

Keywords