Abstract
The ubiquitin-proteasome pathway plays a central role in the degradation of proteins involved in several pathways including the cell cycle, cellular proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to enter clinical use, and received approval by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma, therefore validating inhibition of the proteasome as an anticancer target. The approval of Bortezomib was based on a large, international, multicenter phase III trial showing its efficacy and safety compared with conventional therapy. Preclinical data also demonstrates the synergistic effect of bortezomib with other chemotherapeutic agents and its ability to overcome drug resistance. Since then several other proteasome inhibitors have been developed. The anti-tumor activities of bortezomib have been attributed to its effect on pro-apoptotic pathways including the inhibition of NF-κB and induction of endoplasmic reticulum stress. However, the molecular mechanisms are not fully understood. In this review, we will summarize the molecular mechanism of apoptosis by bortezomib.
Keywords: dependent proteolysis, proteasome, bortezomib-induced apoptosis, cyclin D1
Anti-Cancer Agents in Medicinal Chemistry
Title: Targeting the Ubiquitin-Proteasome Pathway in Cancer Therapy
Volume: 7 Issue: 3
Author(s): Yuki Ishii, Samuel Waxman and Doris Germain
Affiliation:
Keywords: dependent proteolysis, proteasome, bortezomib-induced apoptosis, cyclin D1
Abstract: The ubiquitin-proteasome pathway plays a central role in the degradation of proteins involved in several pathways including the cell cycle, cellular proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to enter clinical use, and received approval by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma, therefore validating inhibition of the proteasome as an anticancer target. The approval of Bortezomib was based on a large, international, multicenter phase III trial showing its efficacy and safety compared with conventional therapy. Preclinical data also demonstrates the synergistic effect of bortezomib with other chemotherapeutic agents and its ability to overcome drug resistance. Since then several other proteasome inhibitors have been developed. The anti-tumor activities of bortezomib have been attributed to its effect on pro-apoptotic pathways including the inhibition of NF-κB and induction of endoplasmic reticulum stress. However, the molecular mechanisms are not fully understood. In this review, we will summarize the molecular mechanism of apoptosis by bortezomib.
Export Options
About this article
Cite this article as:
Ishii Yuki, Waxman Samuel and Germain Doris, Targeting the Ubiquitin-Proteasome Pathway in Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (3) . https://dx.doi.org/10.2174/187152007780618180
DOI https://dx.doi.org/10.2174/187152007780618180 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Gene Transfer to the Central Nervous System: Current State of the Art of the Viral Vectors
Current Genomics Dual Targeting of Glioma U251 Cells with Nanoparticles Prevents Tumor Angiogenesis and Inhibits Tumor Growth
Current Neurovascular Research Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers
Recent Patents on Anti-Infective Drug Discovery The Arrestin Fold: Variations on a Theme
Current Genomics Cancer and Stem Cells
Current Cancer Therapy Reviews Rho GTPase Effector Functions in Tumor Cell Invasion and Metastasis
Current Drug Targets Ultrasound-Mediated Cancer Therapeutics Delivery using Micelles and Liposomes: A Review
Recent Patents on Anti-Cancer Drug Discovery Major Developments in the Design of Inhibitors along the Kynurenine Pathway
Current Medicinal Chemistry Pharmacological Inhibition of Poly(ADP-ribose) Polymerase (PARP) Activity in PARP-1 Silenced Tumour Cells Increases Chemosensitivity to Temozolomide and to a N3-Adenine Selective Methylating Agent
Current Cancer Drug Targets The Role of PEDF in Tumor Growth and Metastasis
Current Molecular Medicine Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Active Targeting Towards and Inside the Brain based on Nanoparticles: A Review
Current Pharmaceutical Biotechnology Apoptosis Induction by Ultrasound and Microbubble Mediated Drug Delivery and Gene Therapy
Current Molecular Medicine Anticancer Drug Combinations, How Far We can Go Through?
Anti-Cancer Agents in Medicinal Chemistry The Role of XRCC4 in Carcinogenesis and Anticancer Drug Discovery
Recent Patents on Anti-Cancer Drug Discovery Eph Receptors as Drug Targets: Single-Chain Antibodies and Beyond
Current Drug Targets Interlinking of Hypoxia and Estrogen in Thyroid Cancer Progression
Current Medicinal Chemistry Chemical and Radiochemical Considerations in Radiolabeling with α-Emitting Radionuclides
Current Radiopharmaceuticals Dynamic Contrast-Enhanced MRI in Oncology Drug Development
Current Clinical Pharmacology Magnetic Resonance Nano-Theranostics for Glioblastoma Multiforme
Current Pharmaceutical Design