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Bortezomib in the Treatment of Cancer

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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-κB), 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 antiangiogenic 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.

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Keywords: Bortezomib; anti-tumor activity; proteasome inhibition

Document Type: Research Article

Affiliations: Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico, 70124 Bari, Italy.

Publication date: November 1, 2006

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  • Recent Patents on Anti-Cancer Drug Discovery publishes review articles on recent patents in the field of anti-cancer drug discovery e.g. novel bioactive compounds, analogs & targets. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery.
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