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Nuclear transport inhibition in acute myeloid leukemia: recent advances and future perspectives

Chetasi Talati1, Kendra L Sweet1

  • 1Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, 33611, USA.

International Journal of Hematologic Oncology
|November 9, 2018
PubMed

Insights

Selective inhibitors of nuclear export (SINE) offer a new way to treat acute myeloid leukemia by blocking Exportin 1. This approach shows promise in overcoming chemotherapy resistance and has shown antileukemic activity in early trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Selective inhibitors of nuclear export (SINE) represent a novel therapeutic strategy for acute myeloid leukemia (AML).
  • These inhibitors target Exportin 1 (chromosomal region maintenance 1), a key protein in nuclear-cytoplasmic transport.
  • Overcoming resistance to conventional chemotherapy is a critical challenge in AML treatment.

Purpose of the Study:

  • To discuss the mechanism of action of SINEs in the context of AML.
  • To review the clinical data of SINEs, specifically selinexor, in AML treatment.
  • To highlight the potential of SINEs in overcoming chemotherapy resistance in AML.

Main Methods:

  • Review of scientific literature on SINEs and their mechanism of action.
  • Analysis of preclinical and clinical data from studies involving SINEs in AML.
  • Discussion of the role of Exportin 1 inhibition in cancer therapy.

Main Results:

  • SINEs effectively block Exportin 1, leading to nuclear retention of tumor suppressor proteins.
  • Selinexor, a first-generation SINE, demonstrates promising antileukemic and pro-apoptotic activity in early clinical studies.
  • SINEs show potential in overcoming resistance to conventional chemotherapy in AML.

Conclusions:

  • SINEs, by inhibiting Exportin 1, offer a promising therapeutic avenue for AML.
  • Clinical trials involving selinexor indicate significant antileukemic effects.
  • Further investigation into SINEs is warranted to establish their role in AML treatment strategies.
Keywords:
CRM1 inhibitorKPT-8602XPO1 inhibitoracute myeloid leukemianuclear transport inhibitorselinexor

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