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Bortezomib in the treatment of cancer
Aldo M Roccaro1, Angelo Vacca, Domenico Ribatti
1Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Abstract:
Bortezomib (Velcade, formerly PS-341) represents the first proteasome inhibitor to have shown anti-tumor activity in both solid and haematological malignancies. It blocks activation of nuclear factor-kappa B (NF-kB), resulting in increased apoptosis, decreased angiogenic cytokine production, and inhibition of tumor cell adhesion to stroma. Additional mechanisms of action include c-Jun N-terminal kinase activation, effects on growth factor expression and anti-angiogenic properties. Multiple myeloma is the prototype of cancer where bortezomib has shown marked in vitro activity, which was followed by rapid translation to phase I, II and III clinical trials, and resulted in accelerated approval by the FDA for the treatment of patients with relapsed refractory disease. Different clinical trials are currently ongoing in multiple myeloma as well as in many others haematologic and solid tumors (mantle cell and follicular non-Hodgkin's lymphoma; peripheral T-cell lymphoma; Waldenström's macroglobulinemia, chronic lymphocytic leukemia; head and neck / gastroesophageal junction / stomach /colo-rectal / prostate / non-small cell lung cancer). This reviews focuses on the proteasome inhibition exerted by bortezomib, the first proteasome inhibitor to have shown anti-cancer activity in both solid and haematologic malignancies.
Insights
Bortezomib is the first proteasome inhibitor with anti-tumor effects in solid and blood cancers. It works by blocking nuclear factor-kappa B (NF-kB) activation, leading to cancer cell death and reduced tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Bortezomib (Velcade) is the pioneering proteasome inhibitor demonstrating significant anti-tumor activity.
- It targets the proteasome, a crucial cellular complex involved in protein degradation.
Purpose of the Study:
- To review the mechanisms of action of bortezomib as a proteasome inhibitor.
- To highlight its efficacy in various hematologic and solid malignancies.
- To discuss its clinical applications and ongoing trials.
Main Methods:
- Review of preclinical and clinical studies on bortezomib.
- Analysis of bortezomib's molecular targets and signaling pathways.
- Examination of clinical trial data for efficacy and safety.
Main Results:
- Bortezomib inhibits nuclear factor-kappa B (NF-kB) activation, promoting apoptosis.
- It reduces angiogenic cytokine production and tumor cell adhesion.
- Demonstrated efficacy in multiple myeloma, leading to FDA approval for relapsed refractory disease.
Conclusions:
- Bortezomib is a key therapeutic agent targeting the proteasome pathway.
- Its broad anti-cancer activity extends to various hematologic and solid tumors.
- Ongoing research continues to explore its potential in diverse oncological settings.
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