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Targeting the Ubiquitin-Proteasome System for Cancer
Zhaoyun Liu1, Jiao Lai1, Ziyu Ma1
1Department of Hematology Tianjin Medical University General Hospital Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control Tianjin Institute of Hematology State Key Laboratory of Experimental Hematology Tianjin China.
Abstract:
Ubiquitin is a highly conserved small molecule that exists in large quantities in eukaryotic cells and plays a crucial role in protein quality control by phagocytosis and degradation of ubiquitin-modified proteins. The abnormal expression of the ubiquitin-proteasome system (UPS) in cancer leads to the abnormal expression of ubiquitin ligases and ubiquitin-binding enzymes, resulting in the abnormal accumulation of ubiquitinated proteins. Consequently, UPS dysregulation can contribute to tumor initiation, progression, and resistance to therapy. While proteasome inhibitors have shown clinical success, comprehensive reviews integrating upstream UPS components and their therapeutic potential are lacking. This paper reviews the composition of the UPS, its tumor-promoting mechanisms, as well as the small molecule inhibitors and proteasome inhibitors based on this system, including their mechanisms of action and adverse effects, and explores their clinical advances in the treatment of cancer. This review provides a valuable framework for developing next-generation anti-cancer therapies and establishes the UPS as a critical therapeutic target for precision oncology.
Insights
The ubiquitin-proteasome system (UPS) is crucial for protein control and its dysregulation drives cancer. Targeting UPS components offers a promising strategy for novel anti-cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The ubiquitin-proteasome system (UPS) regulates protein homeostasis and degradation.
- UPS dysregulation, including abnormal ubiquitin ligases and enzymes, promotes cancer initiation, progression, and therapeutic resistance.
- Existing treatments like proteasome inhibitors show promise, but a comprehensive review of upstream UPS components is needed.
Purpose of the Study:
- To review the composition and tumor-promoting mechanisms of the UPS.
- To analyze small molecule and proteasome inhibitors targeting the UPS.
- To explore the clinical advances of UPS-based therapies in cancer treatment.
Main Methods:
- Literature review of UPS composition and function in cancer.
- Analysis of small molecule and proteasome inhibitors targeting the UPS.
- Examination of clinical trial data for UPS-targeted cancer therapies.
Main Results:
- The UPS plays a significant role in cancer development and progression.
- Various small molecule and proteasome inhibitors targeting the UPS have been developed.
- Clinical studies demonstrate the therapeutic potential of UPS-targeted agents in cancer.
Conclusions:
- The UPS is a critical therapeutic target for precision oncology.
- Targeting the UPS offers a promising framework for developing next-generation anti-cancer therapies.
- Further research into upstream UPS components can enhance therapeutic strategies.
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