Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.
The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level.
Russo
Antonio
A
Universita' di Palermo, Section of Medical Oncology, Department of Surgical and Oncological Sciences, Italy.
Fratto
Maria E
ME
Bazan
Viviana
V
Schiró
Valentina
V
Agnese
Valentina
V
Cicero
Giuseppe
G
Vincenzi
Bruno
B
Tonini
Giuseppe
G
Santini
Daniele
D
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; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011719:Pyrazines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib