Related Experiment Video

Updated: Aug 24, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

The development of proteasome inhibitors as anticancer drugs

Julian Adams1

  • 1Infinity Pharmaceuticals, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA. julian.adams@ipi.com

Cancer Cell
|May 18, 2004
PubMed

Insights

Proteasome inhibition is a promising anticancer therapy targeting cellular protein destruction. Bortezomib, the first proteasome inhibitor, showed efficacy in multiple myeloma patients, leading to its approval.

Area of Science:

  • Cellular Biology
  • Oncology
  • Pharmacology

Background:

  • The ubiquitin-proteasome pathway regulates cellular protein levels, crucial for cell proliferation and survival.
  • Cancer cells rely on this pathway, making proteasome inhibition a viable anticancer strategy.
  • Bortezomib emerged as the first proteasome inhibitor for clinical investigation due to its cytotoxic effects.

Purpose of the Study:

  • To evaluate the efficacy and safety of bortezomib as a proteasome inhibitor in cancer therapy.
  • To assess bortezomib's role in treating relapsed and refractory multiple myeloma.

Main Methods:

  • Phase 2 clinical trial evaluating bortezomib's efficacy and safety.
  • Treatment of patients with relapsed and refractory multiple myeloma.

Main Results:

  • Bortezomib demonstrated encouraging cytotoxic activity.
  • Positive efficacy and safety results were observed in the phase 2 trial.
  • Bortezomib gained approval for specific multiple myeloma patient populations.

Conclusions:

  • Proteasome inhibition, exemplified by bortezomib, is an effective therapeutic approach for certain cancers.
  • Bortezomib is approved for patients with relapsed/refractory multiple myeloma after at least two prior therapies and disease progression.

More Related Videos

A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer10:46

A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer

Published on: September 13, 2022

Related Concept Videos

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 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...
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...
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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...