title: Bortezomib in the treatment of cancer.
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.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010330:Patents as Topic; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib