Selective Inhibitors of Nuclear Export in the Treatment of Hematologic Malignancies

Clin Lymphoma Myeloma Leuk. 2019 Nov;19(11):689-698. doi: 10.1016/j.clml.2019.08.011. Epub 2019 Aug 29.

Abstract

The correct localization of molecules between nucleus and cytoplasm is fundamental for cellular homeostasis and is controlled by a bidirectional transport system. Exportin 1 (XPO1) regulates the passage of numerous cancer-related proteins. In this review, we summarize the development of a novel class of antitumor agents, known as selective inhibitors of nuclear export (SINEs). We report results of preclinical studies and clinical trials, and discuss the mechanism of action of SINEs and their effects in multiple myeloma, non-Hodgkin lymphomas, lymphoblastic leukemia, and acute and chronic myeloid leukemia. In the future, the numerous experimental studies currently underway will allow us to define the role of SINEs and will possibly permit these substances to be introduced into daily clinical practice.

Keywords: Exportin 1; Karyopherins; Leukemia; Multiple myeloma; Selinexor.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus / drug effects*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers
  • Clinical Studies as Topic
  • Cytoplasm / metabolism
  • Drug Evaluation, Preclinical
  • Exportin 1 Protein
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / etiology
  • Hematologic Neoplasms / metabolism
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • Molecular Targeted Therapy
  • Nuclear Pore / metabolism
  • Prognosis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear