Related Experiment Video

Updated: Aug 13, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Targeting the proteasome as a therapeutic strategy against haematological malignancies

Robert Z Orlowski1, Erik L Zeger

  • 1Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA. R_Orlowski@med.unc.edu

Expert Opinion on Investigational Drugs
|January 26, 2006
PubMed

Insights

Bortezomib, a proteasome inhibitor, shows anti-cancer effects by blocking cell growth and promoting cell death. Clinical trials confirm its efficacy in multiple myeloma and potential in other blood cancers, alone or combined with chemotherapy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • The ubiquitin-proteasome pathway regulates intracellular protein degradation.
  • Proteasome inhibition offers anti-tumour effects, including cell-cycle arrest, apoptosis induction, and anti-angiogenesis.
  • Bortezomib is the first clinically approved proteasome inhibitor.

Purpose of the Study:

  • To review the clinical activity of bortezomib in hematological malignancies.
  • To evaluate bortezomib's efficacy as a single agent and in combination therapies.
  • To explore bortezomib's role in overcoming chemoresistance.

Main Methods:

  • Review of Phase I-III clinical trials data for bortezomib.
  • Analysis of bortezomib's efficacy in multiple myeloma and non-Hodgkin's lymphoma.
  • Assessment of combination regimens involving bortezomib and standard chemotherapeutics.

Main Results:

  • Bortezomib demonstrated verified activity against relapsed/refractory multiple myeloma.
  • Encouraging single-agent activity was observed in non-Hodgkin's lymphoma.
  • Combination therapies with bortezomib have shown enhanced efficacy in ongoing studies.

Conclusions:

  • Bortezomib is an effective treatment for multiple myeloma and shows promise in other hematological malignancies.
  • Proteasome inhibition is a key strategy for overcoming chemoresistance and enhancing treatment efficacy.
  • Further research is ongoing to establish bortezomib's role in front-line therapy and various combination regimens.

More Related Videos

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

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

Published on: May 15, 2019

Related Concept Videos

The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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.
There are several types of targeted therapies against specific...
The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...