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Related Concept Videos

Nuclear Export01:42

Nuclear Export

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
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Related Experiment Video

Updated: Oct 4, 2025

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Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.

Shambavi Richard1, Sundar Jagannath2

  • 1Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1185, New York, NY, 10029, USA.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
|February 3, 2022
PubMed
Summary

Selinexor, a selective inhibitor of nuclear export (SINE) protein XPO1, shows efficacy in treating multiple myeloma. Clinical trials demonstrate its effectiveness, particularly in combination therapies, with ongoing research for improved tolerability.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Overexpression of exportin-1 (XPO1) is linked to poor prognosis in multiple myeloma.
  • XPO1 facilitates the nuclear export of tumor suppressors, promoting cancer growth.

Purpose of the Study:

  • To evaluate the efficacy and safety of selinexor, a novel oral selective inhibitor of nuclear export (SINE), in multiple myeloma treatment.
  • To explore selinexor's potential as a single agent and in combination therapies for relapsed refractory multiple myeloma (RRMM).

Main Methods:

  • Clinical trials (STORM, STOMP, BOSTON) assessed selinexor's efficacy and safety in patients with multiple myeloma.
  • Preclinical studies investigated selinexor and other SINE compounds in tumor cell lines and animal models.

Main Results:

  • Selinexor demonstrated significant response rates in penta-refractory myeloma and superiority in combination with bortezomib and dexamethasone for RRMM.
  • The STORM trial led to FDA approval of selinexor with dexamethasone for refractory myeloma.
  • Ongoing trials are evaluating combinations and new SINE compounds like eltanexor for better tolerability.

Conclusions:

  • Selinexor is an effective therapeutic agent for multiple myeloma, offering a new treatment option.
  • Combination therapies involving selinexor show promising results in RRMM.
  • Further research into SINE compounds aims to improve treatment tolerability and outcomes in multiple myeloma.