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Updated: Jul 5, 2026
Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
The potential of proteasome inhibitors in cancer therapy
Jan Sterz1, Ivana von Metzler, Jens-Claus Hahne
1Charité-Universitätsmedizin Berlin, Department of Hematology and Oncology, Charité-Platz 1, 10117 Berlin, Germany.
Background:
The ubiquitin-proteasome system has become a promising novel molecular target in cancer due to its critical role in cellular protein degradation, its interaction with cell cycle and apoptosis regulation and its unique mechanism of action.
Objective:
This review focuses both on preclinical results and on data from clinical trials with proteasome inhibitors in cancer.
Methods:
Results in hematological malignancies and solid tumors were included, and important data presented in abstract form were considered in this review.
Results/Conclusion:
Bortezomib as first-in-class proteasome inhibitor has proven to be highly effective in some hematological malignancies, overcomes conventional chemoresistance, directly induces cell cycle arrest and apoptosis, and also targets the tumor microenvironment. It has been granted approval by the FDA for relapsed multiple myeloma, and recently for relapsed mantle cell lymphoma. Combination chemotherapy regimens have been developed providing high remission rates and remission quality in frontline treatment or in the relapsed setting in multiple myeloma. The combination of proteasome inhibition with novel targeted therapies is an emerging field in oncology. Moreover, novel proteasome inhibitors, such as NPI-0052 and carfilzomib, have been developed. This review summarizes our knowledge of the ubiquitin-proteasome system and recent data from cancer clinical trials.
Insights
The ubiquitin-proteasome system is a key target in cancer therapy. Proteasome inhibitors like bortezomib show efficacy in hematological malignancies and are advancing in clinical trials for various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- The ubiquitin-proteasome system (UPS) is crucial for cellular protein degradation.
- UPS regulates critical processes including cell cycle progression and apoptosis.
- UPS dysfunction is implicated in cancer development and progression.
Purpose of the Study:
- To review preclinical and clinical data on proteasome inhibitors in cancer treatment.
- To summarize the role of the UPS in oncology.
- To highlight recent advancements and emerging therapies targeting the UPS.
Main Methods:
- Systematic review of preclinical studies.
- Analysis of data from clinical trials in hematological malignancies and solid tumors.
- Inclusion of data presented in abstract form.
Main Results:
- Bortezomib, a proteasome inhibitor, is effective in hematological malignancies, overcoming chemoresistance.
- Bortezomib induces cell cycle arrest, apoptosis, and impacts the tumor microenvironment.
- FDA approval for bortezomib in multiple myeloma and mantle cell lymphoma.
- Combination therapies with proteasome inhibitors show high remission rates.
- Novel proteasome inhibitors like NPI-0052 and carfilzomib are under development.
Conclusions:
- Proteasome inhibitors represent a significant therapeutic strategy in oncology.
- Bortezomib has demonstrated clinical success and expanded indications.
- Combination therapies and novel agents offer promising future directions.
- Targeting the UPS is a validated approach for cancer treatment.
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