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Selective inhibitors of nuclear export (SINE) in hematological malignancies

Arundhati Das1, Guoqing Wei2, Kaushal Parikh1

  • 1Department of Medicine, Westchester Medical Center, Valhalla, NY 10595 USA.

Experimental Hematology & Oncology
|March 7, 2015
PubMed

Insights

CRM1, crucial for cell balance, exports tumor suppressor proteins and is overexpressed in cancers. Selective inhibitors of nuclear exportins (SINEs) are emerging as novel anti-cancer agents, particularly for hematological malignancies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Nucleo-cytoplasmic transport is vital for cellular homeostasis.
  • CRM1 (exportin 1) mediates the transport of over 200 proteins, including tumor suppressors.
  • CRM1 overexpression is implicated in various cancers, including hematological malignancies.

Purpose of the Study:

  • To review the role of CRM1 in carcinogenesis.
  • To discuss the development of selective inhibitors of nuclear exportins (SINEs).
  • To highlight SINEs' potential in treating hematological malignancies.

Main Methods:

  • Literature review focusing on CRM1 function and SINE development.
  • Analysis of CRM1's role in cancer progression.
  • Examination of SINEs as therapeutic agents.

Main Results:

  • CRM1 is a key regulator of protein transport and its dysregulation contributes to cancer.
  • Selective inhibitors of nuclear exportins (SINEs) represent a promising new class of anti-cancer drugs.
  • Selinexor (KPT-330) is the first-in-human SINE agent, showing potential in hematological malignancies.

Conclusions:

  • Targeting CRM1-mediated nuclear export is a viable anti-cancer strategy.
  • SINEs offer a novel therapeutic approach for hematological cancers.
  • Further research into SINEs is warranted for broader cancer applications.
Keywords:
KPT-330SINESelective inhibitor of nuclear exportSlinexor

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