Related Experiment Video
Updated: Mar 4, 2026
Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
Proteasome inhibition and its therapeutic potential in multiple myeloma
Ajai Chari1, Amitabha Mazumder, Sundar Jagannath
1Mount Sinai School of Medicine, New York, NY, USA.
Abstract:
Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years. In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease. In this article, we briefly review the preclinical and clinical development of the drug as the underpinning for a systematic review of the large number of clinical trials that are beginning to shed some light on the full therapeutic potential of bortezomib in myeloma. We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.
Insights
Bortezomib, a proteasome inhibitor, offers new hope for multiple myeloma treatment. Ongoing research explores its mechanism and potential alongside novel proteasome inhibitors for improved patient outcomes.
Area of Science:
- Oncology
- Pharmacology
Background:
- Multiple myeloma lacks effective treatments, creating an unmet clinical need.
- Bortezomib, a novel proteasome inhibitor, was rapidly approved for multiple myeloma.
- Questions remain regarding bortezomib's mechanism of action, toxicity, and optimal use.
Purpose of the Study:
- To review the preclinical and clinical development of bortezomib.
- To systematically review clinical trials assessing bortezomib's therapeutic potential in multiple myeloma.
- To discuss the current understanding of bortezomib's mechanism and future proteasome inhibitors.
Main Methods:
- Review of preclinical data.
- Systematic review of clinical trials.
- Literature review of mechanism of action and novel agents.
Main Results:
- Bortezomib demonstrated rapid FDA approval, indicating significant clinical impact.
- Clinical trials are beginning to elucidate the full therapeutic potential of bortezomib.
- Understanding bortezomib's mechanism is crucial for future treatment strategies.
Conclusions:
- Bortezomib represents a significant advancement in multiple myeloma treatment.
- Further research into bortezomib's mechanism and novel proteasome inhibitors is essential.
- Proteasome inhibition holds substantial promise for managing multiple myeloma.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:18The Proteasome
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...
01:13The Proteasome
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...
02:18The Proteasome
02:50Combination Therapies and Personalized Medicine
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...
02:23Abnormal Proliferation