Proteasome Inhibitors as a Potential Cause of Heart Failure
Georgios Koulaouzidis1, Alexander R Lyon2
1NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London SW3 6NP, UK.
Abstract:
Proteasome inhibitors have become an important drug class in the treatment of multiple myeloma. In addition to its role in myeloma cells, the proteasome plays a critical role in the myocardium, particularly in the context of cardiac stress. The growing awareness of the cardiovascular toxicity of proteasome inhibitors is emerging following the phase 3 trials and the transition into real-world practice. This article reviews the background to this problem and the incidence of the problem in phase 3 trials and subsequent phase 2 trials in new patient cohorts and discusses the strategy to detect and manage this emerging problem.
Insights
Proteasome inhibitors, used for multiple myeloma, can cause cardiac toxicity. This review examines the incidence and management strategies for this emerging cardiovascular issue in patients.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Proteasome inhibitors are crucial in multiple myeloma treatment.
- The proteasome is vital in heart muscle function, especially under stress.
- Cardiovascular toxicity from proteasome inhibitors is an emerging concern.
Purpose of the Study:
- To review the background of proteasome inhibitor-induced cardiotoxicity.
- To report the incidence of cardiotoxicity in clinical trials.
- To discuss detection and management strategies.
Main Methods:
- Review of phase 3 and phase 2 clinical trial data.
- Analysis of real-world practice observations.
- Synthesis of current knowledge on proteasome function in the myocardium.
Main Results:
- Cardiovascular toxicity is an identified side effect of proteasome inhibitors.
- Incidence data from trials highlight the need for monitoring.
- Management strategies are being developed to mitigate cardiac risks.
Conclusions:
- Awareness and proactive management of cardiovascular toxicity are essential for patients on proteasome inhibitors.
- Further research and clinical vigilance are needed.
- Balancing cancer treatment efficacy with cardiac safety is paramount.
Related Concept Videos
01:26Heart Failure Drugs: Inotropic Agents
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
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
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...
01:17Pathophysiology of Heart Failure
01:27Heart Failure I: Introduction