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Related Experiment Video

Updated: May 7, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Why proteasome inhibitors cannot ERADicate multiple myeloma.

Robert Z Orlowski¹

¹Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

|September 14, 2013

Summary

Tumor cells can develop resistance to proteasome inhibitors like bortezomib through poorly understood mechanisms. A new study identifies XBP1s-negative subpopulations as a key factor in bortezomib resistance in multiple myeloma.

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

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Published on: March 23, 2020

Area of Science:

Oncology
Molecular Biology
Cancer Research

Background:

Proteasome inhibitors are crucial for treating multiple myeloma.
Therapeutic resistance limits the effectiveness of these treatments.
Mechanisms underlying resistance are not fully understood.

Purpose of the Study:

To investigate novel mechanisms of therapeutic resistance in multiple myeloma.
To identify specific tumor cell subpopulations responsible for resistance to proteasome inhibitors.

Main Methods:

Analysis of tumor cell subpopulations.
Assessment of bortezomib resistance.
Investigation of the role of X-box binding protein 1 (XBP1) splicing.

Main Results:

Identification of XBP1s-negative tumor cell subpopulations.
Demonstration that these subpopulations exhibit resistance to bortezomib.
Association of these resistant subpopulations with clinical therapeutic failures.

Conclusions:

XBP1s-negative subpopulations contribute to bortezomib resistance in multiple myeloma.
Targeting these specific subpopulations may overcome therapeutic resistance.
Understanding these mechanisms can improve treatment strategies for multiple myeloma.