Back to Search
Start Over
Proteasome: an emerging target for cancer therapy
- Source :
- Anti-cancer drugs. 16(5)
- Publication Year :
- 2005
-
Abstract
- Proteasome inhibitors represent novel anti-cancer drugs which interact with the proteasome-ubiquitin pathway. The 26S proteasome is a multicatalytic threonine protease with three distinct catalytic activities. It is responsible for intracellular protein turnover in eukaryotic cells, including the processing and degradation of short- and some long-living proteins required for regulation of various cellular functions. Subsequently, the inhibition of the proteasomal function results in stabilization and accumulation of its substrates, which notably include cyclins, cyclin-dependent kinase inhibitors, transcriptional factors, tumor suppressor proteins and proto-oncogenes. This results in confounding signals in the cell inducing cell cycle arrest and activation of apoptotic programs. Acting on transcriptional factor NF-kappaB, which is upregulated in some tumors undergoing chemotherapy or irradiation and downregulated by proteasome inhibition, a significant chemosensitization and consequently synergistic effects concerning the anti-tumor activity could be achieved. Bortezomib is the first proteasome inhibitor that has entered clinical trials. In multiple myeloma, both the US Food and Drug Administration and European Medicine Evaluation Agency granted approval for the use of bortezomib (Velcade) for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. At present, other trials examine the activity in a variety of solid tumors and hematological malignancies. This paper reviews preclinical and clinical results.
- Subjects :
- Cancer Research
Proteasome Endopeptidase Complex
Cell cycle checkpoint
Threonine protease
Antineoplastic Agents
Pharmacology
Substrate Specificity
Bortezomib
Neoplasms
medicine
Animals
Humans
Pharmacology (medical)
Protease Inhibitors
Multiple myeloma
Clinical Trials as Topic
business.industry
Kinase
Cancer
medicine.disease
Boronic Acids
Treatment Outcome
Oncology
Proteasome
Pyrazines
Proteasome inhibitor
business
Proteasome Inhibitors
medicine.drug
Subjects
Details
- ISSN :
- 09594973
- Volume :
- 16
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Anti-cancer drugs
- Accession number :
- edsair.doi.dedup.....572026061089f27541eaa6534382e55b